The basic issue is that Python do not have a UI lib of its own, so if you want to do anything beyond a CLI you need to introduce a third party.

I don't really think GTK is that difficult to get a grasp on with composite templates. It's a little less "magic" than VB6 since I'm not just dumping code into a partial form class where the rest of the accessors to the COM controls are generated for me, but it's pretty straightforward in Vala right now (I use glade to design a UI, much like the classic WinForms designer - annotate a class with a GtkTemplate attribute and then put GtkChild attributes on class members to have the widgets automatically assigned there).

In Python it'd look like

    @GtkTemplate("my_window.ui")
    class MyWindow:
        @GtkChild my_textbox
        
        @GtkCallback
        def button_clicked(self, btn):
            my_textbox.text = "Hello, World!"