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Best way to build a cross-platform and custom-skinned application with Python

Features needed:
A framework, allowing me to build tab-based application with custom design (like in Hotot twitter client), keeping the native os window frame.
Compatible with Python.
My application will be running under Win/OsX/Linux/.
No Flash/Flex/AIR.
I also would like to ask if PySide does meet my requirements and is it worse or better than wxPython and Tkinter mentioned already?

Use Tkinter. It works on every platform that Python supports, is relatively easy to program in, looks pretty good on most platforms, and has the features you want. It's also built-in for most versions of Python, so your users (in many cases) will not have to install any external dependencies.
I find that Tkinter looks best on Mac OSX and Windows, and slightly outdated on some Gnome desktops. The most important feature, however, is that the API is extremely clean and easy to use and it is very lightweight. PyQt has a similar feature set, but, in my experience, its performance is significantly degraded when compared to Tkinter.
PySide is Nokia's Qt binding for Python. I'm not aware of what the differences are between it and PyQt. Ultimately, most GUI toolkits for Python are going to be cross platform and support the functionality you need. I suggest Tkinter because I feel it is the easiest and most pleasurable way to program GUI applications in Python.

I am the author of Hotot.
according to your requirements, the key for you to choose a framework is the UI framework should be able to access webview conveniently.
Hotot has several wrappers for different platforms. On Linux, we have both Qt and GTK version, on Windows, we provide a Qt version, on Mac, we have a Cocoa version, and of course we have a Chrome version. In a word, all they can easily access webkit.
PS: XULRunner is another good choice for native appearance.

Additionally to the advices given by other people, I suggest you to use PyQt which is a Python binding to Qt framework. It's widely used, cross-platform and feature-full.

Take a look at wxPython (based on wxWidgets). If you want to make it web-based, look into using Django.

Well, you mentioned PyHotOt, and it says (on its web site) that it uses pywebkitgtk, and PyGTK. PyGTK/PyWebKitGTK exists for windows. Did you check it out? I think OS X would be the weak link on GTK, but maybe it's pretty good too.

Python GUI(tkinter; pygtk+glade), py2exe

I'm new with python programming and GUI. I search on internet about GUI programming and see that there are a lot of ways to do this. I see that easiest way for GUI in python might be tkinter(which is included in Python, and it's just GUI library not GUI builder)? I also read a lot about GLADE+PyGTK(and XML format), what is there so special(glade is GUI builder)?
Can anyone make some "personal opinion" about this choices?
I have python code, I need to make simple GUI(2 button's-open-close-read-write,and some "print" work) and then make some .exe file (is there best choice py2exe=?). Is there a lot of changes in code to make GUI?
Many thanks

If your GUI is really that simple, you should go with the built-in tkinter.
There's a Hello, Tkinter tutorial that you can follow, it's pretty straightforward. Concerning the creation of executables, py2exe should work without problems in most cases (though I haven't tried with tkinter). Another way to create an executable is to add a special parameter to your "setup.py" file:
setup(...,
entry_points = {"gui_scripts" : ['name-of-executable = name_of_package.launcher:main']})
This would, for example, create an executable that can be run by typing "name-of-executable" into a terminal (even on Windows if Python's "scripts" path is in the PATH ^^). It runs the function "main" in the module called "name_of_package". That way, you don't have to use py2exe but can create a Windows installer, or a Debian package, for instance.
For more complex projects, I can absolutely recommend PyGTK with Glade as interface designer. It requires several Python packages to be installed, plus a GTK+ installation (which is not always that easy on Windows). The API is awesome, well-documented and Glade is very easy to use, once you get used to the layouting concepts of GTK. But my opinion is kind of biased because I've done multiple projects in PyGTK. wxWidgets or PyQT are good alternatives. For example, bazaar explorer is written using QT.

I really like PyQt bindings for Qt library.
What is PyQt?
Qt itself is a very nice framework - rich, powerfull, elegant (for my taste, at least). And PyQt does a very nice job of exposing that functionality to a scripting environment.
Plus, there is a very nice book about PyQt development - Rapid GUI Programming with Python and Qt - working through it helped me a lot.

Help On Python program that can use to compile python coding into a standalone .exe file

I am currently working on a python program with the use of wxpython to make out a gui application. However, i wish to compile my application to be like a standalone application where people can just get the .exe file and run it without installing python and wxpython. I am not sure if it is possible, thus i hope that someone can give me some guidance on this. Also, if it is possible, please tell me what program should i use to accomplish that.
Thanks

You need to create a frozen binary. You can use py2exe for this purpose.
For what it's worth, if you ever need to make executables on a unix system, you can use Freeze, a utility that comes with Python.

For a nice cross-platform solution, I always recommend pyinstaller (actually, I find it better than py2exe even just for making a Windows-only executable -- it can do code signing, can seamlessly incorporate "big, hairy" libraries such as PyQt, etc;-).

Python GUI Application redistribution

I need to develop a small-medium sized desktop GUI application, preferably with Python as a language of choice because of time constraints.
What GUI library choices do I have which allow me to redistribute my application standalone, assuming that the users don't have a working Python installation and obviously don't have the GUI libraries I'm using either?
Also, how would I go about packaging everything up in binaries of reasonable size for each target OS? (my main targets are Windows and Mac OS X)
Addition:
I've been looking at WxPython, but I've found plenty of horror stories of packaging it with cx_freeze and getting 30mb+ binaries, and no real advice on how to actually do the packaging and how trust-worthy it is.

http://wiki.wxpython.org/CreatingStandaloneExecutables
It shouldn't be that large unless you have managed to include the debug build of wx.
I seem to rememebr about 4Mb for the python.dll and similair for wx.

This may help:
How can I make an EXE file from a Python program?

Python has an embedded GUI toolkit named TKinter which is based on Tk library from TCL programming language. It is very basic and does not have all the functionality you expect in Windows Forms or GTK for example but if you must have platform independent toolkit I see no other choice taking in mind that you also dont want to grow that much the binary.
Tkinter is not hard at all to use since it doesnt have millions of widgets/controls and options and is the default toolkit included in most python distributions, at least on Windows, OSX and Linux.
GTK and QT are prettier and more powerful but they have a one big disadvantage for you: they are heavy and deppend upon third libraries, especially GTK which has a lot of dependencies that makes it a little hard to distribute it embeded in your software.
As for the binary creation I know there is py2exe which converts python code to win32 executable code (.exe's) but im not sure if there is something similar for OSX. Are you worried because people could see the source code or just so you can bundle all in a single package? If you just want to bundle everything you dont need to create a standalone executable, you could easily create an installer:
Creating distributable in python
That's a guide on how to distribute your software when it's done.

http://Gajim.org for Windows uses python and PyGtk. You can check, how they did it. Also, there's PyQt for GUI (and wxpython mentioned earlier).

I don't have any experience building stand-alone apps for any platform other than Windows.
That said:
Tkinter: works fine with py2exe. Python Megawidgets (an "expansion library" for Tkinter) works fine also, but it does funky things with dynamic imports, so you need to combine all the components into a big file "pmw.py" and add it to your project (well, you'll also have pmwblt.py and pmwcolor.py). There are instructions for how to do this somewhere (either on py2exe wiki or in the PMW docs). Tix (an extension to Tk that you can use with Tkinter) doesn't work with py2exe, or at least that was my experience about four years ago.
wxPython also works fine with py2exe. I just checked an app I have; the whole distribution came to around 11MB. Most of that was the wx DLLs and .pyd files, but I can't see how you'd avoid that. If you are targetting Windows XP, you need to include a manifest in your setup.py or else it will look ugly. See this email for details.

I've used py2Exe myself - it's really easy (at least for small apps).

Combination that I am familiar with: wxPython, py2exe, upx
The key to resolving your last concern about the size of the distribution is using upx to compress the DLLs. It looks like they support MacOS executables. You will pay an initial decompression penalty when the DLLs are first loaded.

Create a directly-executable cross-platform GUI app using Python

Python works on multiple platforms and can be used for desktop and web applications, thus I conclude that there is some way to compile it into an executable for Mac, Windows and Linux.
The problem being I have no idea where to start or how to write a GUI with it, can anybody shed some light on this and point me in the right direction please?

First you will need some GUI library with Python bindings and then (if you want) some program that will convert your python scripts into standalone executables.
Cross-platform GUI libraries with Python bindings (Windows, Linux, Mac)
Of course, there are many, but the most popular that I've seen in wild are:
Tkinter - based on Tk GUI toolkit (de-facto standard GUI library for python, free for commercial projects)
WxPython - based on WxWidgets (popular, free for commercial projects)
Qt using the PyQt bindings or Qt for Python. The former is not free for commercial projects. The latter is less mature, but can be used for free.
Complete list is at http://wiki.python.org/moin/GuiProgramming
Single executable (all platforms)
PyInstaller - the most active(Could also be used with PyQt)
fbs - if you chose Qt above
Single executable (Windows)
py2exe - used to be the most popular
Single executable (Linux)
Freeze - works the same way like py2exe but targets Linux platform
Single executable (Mac)
py2app - again, works like py2exe but targets Mac OS

Another system (not mentioned in the accepted answer yet) is PyInstaller, which worked for a PyQt project of mine when py2exe would not. I found it easier to use.
http://www.pyinstaller.org/
Pyinstaller is based on Gordon McMillan's Python Installer. Which is no longer available.

An alternative tool to py2exe is bbfreeze which generates executables for windows and linux. It's newer than py2exe and handles eggs quite well. I've found it magically works better without configuration for a wide variety of applications.

There's also PyGTK, which is basically a Python wrapper for the Gnome Toolkit. I've found it easier to wrap my mind around than Tkinter, coming from pretty much no knowledge of GUI programming previously. It works pretty well and has some good tutorials. Unfortunately there isn't an installer for Python 2.6 for Windows yet, and may not be for a while.

Since python is installed on nearly every non-Windows OS by default now, the only thing you really need to make sure of is that all of the non-standard libraries you use are installed.
Having said that, it is possible to build executables that include the python interpreter, and any libraries you use. This is likely to create a large executable, however.
MacOS X even includes support in the Xcode IDE for creating full standalone GUI apps. These can be run by any user running OS X.

For the GUI itself:
PyQT is pretty much the reference.
Another way to develop a rapid user interface is to write a web app,
have it run locally and display the app in the browser.
Plus, if you go for the Tkinter option suggested by lubos hasko
you may want to try portablepy to have your app run on Windows environment
without Python.

I'm not sure that this is the best way to do it, but when I'm deploying Ruby GUI apps (not Python, but has the same "problem" as far as .exe's are concerned) on Windows, I just write a short launcher in C# that calls on my main script. It compiles to an executable, and I then have an application executable.

PySimpleGUI wraps tkinter and works on Python 3 and 2.7. It also runs on Qt, WxPython and in a web browser, using the same source code for all platforms.
You can make custom GUIs that utilize all of the same widgets that you find in tkinter (sliders, checkboxes, radio buttons, ...). The code tends to be very compact and readable.
#!/usr/bin/env python
import sys
if sys.version_info[0] >= 3:
import PySimpleGUI as sg
else:
import PySimpleGUI27 as sg
layout = [[ sg.Text('My Window') ],
[ sg.Button('OK')]]
window = sg.Window('My window').Layout(layout)
button, value = window.Read()
As explained in the PySimpleGUI Documentation, to build the .EXE file you run:
pyinstaller -wF MyGUIProgram.py

!!! KIVY !!!
I was amazed seeing that no one mentioned Kivy!!!
I have once done a project using Tkinter, although they do advocate that it has improved a lot, it still gives me a feel of windows 98, so I switched to Kivy.
I have been following a tutorial series if it helps...
Just to give an idea of how kivy looks, see this (The project I am working on):
And I have been working on it for barely a week now !
The benefits for Kivy you ask? Check this
The reason why I chose this is, its look and that it can be used in mobile as well.

# I'd use tkinter for python 3
import tkinter
tk = tkinter.Tk()
tk.geometry("400x300+500+300")
l = Label(tk,text="")
l.pack()
e = Entry(tk)
e.pack()
def click():
e['text'] = 'You clicked the button'
b = Button(tk,text="Click me",command=click)
b.pack()
tk.mainloop()
# After this I would you py2exe
# search for the use of this module on stakoverflow
# otherwise I could edit this to let you know how to do it
py2exe
Then you should use py2exe, for example, to bring in one folder all the files needed to run the app, even if the user has not python on his pc (I am talking of windows... for the apple os there is no need of an executable file, I think, as it come with python in it without any need of installing it.
Create this file
Create a setup.py
with this code:
from distutils.core import setup
import py2exe
setup(console=['l4h.py'])
save it in a folder
Put your program in the same folder of setup.py
put in this folder the program you want to make it distribuitable:
es: l4h.py
ps: change the name of the file (from l4h to anything you want, that is an example)
Run cmd from that folder (on the folder, right click + shift and choose start cmd here)
write in cmd:>python setup.py py2exe
in the dist folder there are all the files you need
you can zip it and distribute it
Pyinstaller
Install it from cmd
**
pip install pyinstaller
**
Run it from the cmd from the folder where the file is
**
pyinstaller file.py
**
Update
Read this post to make an exe on windows with pyinstaller the proper way and with one file and images in it https://pythonprogramming.altervista.org/auto-py-to-exe-only-one-file-with-images-for-our-python-apps/

You don't need to compile python for Mac/Windows/Linux. It is an interpreted language, so you simply need to have the Python interpreter installed on the system of your choice (it is available for all three platforms).
As for a GUI library that works cross platform, Python's Tk/Tcl widget library works very well, and I believe is sufficiently cross platform.
Tkinter is the python interface to Tk/Tcl
From the python project webpage:
Tkinter is not the only GuiProgramming
toolkit for Python. It is however the
most commonly used one, and almost the
only one that is portable between
Unix, Mac and Windows

You can use appJar for basic GUI development.
from appJar import gui
num=1
def myfcn(btnName):
global num
num +=1
win.setLabel("mylabel", num)
win = gui('Test')
win.addButtons(["Set"], [myfcn])
win.addLabel("mylabel", "Press the Button")
win.go()
See documentation at appJar site.
Installation is made with pip install appjar from command line.

There's three things you could do:
The first thing is to find a GUI Designer that can launch its code as standalone applications like .exe files. I use a version of MatDeck (for people using GUI Designers I recommend MD Python Designer) as I believe(I use another version so I'm not too sure.) it allows me to convert the code to a standalone applications and by having it as such, there is no need to install the software on every PC that's going to run the program.
The second option is partially bypassing the problem, launch the GUI as a web page. This would give you the most compatibility as most if not all OS can utilize it. Once again, you would need a GUI Designer that can convert its components into a web compatible format, I've done it once and I used the same version of MatDeck(Visionary Deck), I would not recommend MD Python Designer this time as I don't know if it can turn its GUIs into websites using web assembly whereas Visionary Deck I've tried and tested. As with all things there are most likely other software this is just one I use frequently because I work a lot with Mathematics and Physics.
The third option is also kind of bypassing the problem but do it in Tkinter and just ensure you have a Python IDE or just plain old Python and run the code, this will launch the GUI. This is a good solution and maybe the simplest but I wouldn't class it as the shortest or the best. If you only plan to switch between a few operating systems and computers this will probably be your best bet.