Short answer: there’s no single “best” GUI library for all Python projects. Pick based on your target platforms, licensing, look-and-feel, and how complex your UI is. Here’s the pragmatic rundown and when I’d choose each.

The quick verdicts

• PySide6 / PyQt6 (Qt) — Best all-rounder for desktop apps.
  Rich widgets, great designer tools, excellent docs, high polish, theming, high-DPI, accessibility.
  Choose if: you want professional, complex UIs on Windows/macOS/Linux.
  Gotchas: PyQt is GPL/commercial; PySide (LGPL) is friendlier for closed-source.
• Tkinter — Best for tiny tools and teaching.
  Batteries-included (ships with Python), dead-simple API.
  Choose if: you need a quick utility or classroom demos.
  Gotchas: looks dated; limited widgets/layout flexibility.
• wxPython — Best native look on each OS.
  Wraps native controls (Win32, Cocoa, GTK) for true native feel.
  Choose if: native look trumps everything and you’re desktop-only.
  Gotchas: fewer modern components than Qt; packaging can be fiddly.
• Kivy — Best for touch/mobile-ish UIs and OpenGL rendering.
  Cross-platform (desktop, Raspberry Pi, Android, iOS).
  Choose if: you want gesture/touch, animations, or to target Android/iOS with one codebase.
  Gotchas: not native look; steeper layout/styling learning curve.
• Dear PyGui — Best for real-time tools, dashboards, and game-adjacent UIs.
  GPU-accelerated, immediate-mode GUI, great for live plots and inspectors.
  Choose if: performance and custom rendering > native look.
  Gotchas: unconventional model; smaller widget set vs. Qt.
• PySimpleGUI — Fastest way from zero to something clickable.
  Thin wrapper over Tk/Qt/Wx (you pick backend).
  Choose if: you want a simple form/dialog app fast.
  Gotchas: you’ll hit ceilings for complex layouts/behaviors.
• Flet / Toga / pywebview (web-tech UIs) — Best if you prefer web styling.
  Flet uses Flutter concepts in Python; Toga (BeeWare) aims native; pywebview lets you host a web app in a native window.
  Choose if: you’re comfortable with HTML/CSS/JS paradigms or want cross-platform via web tech.
  Gotchas: younger ecosystems; packaging/footprint considerations.

How to choose (decision mini-tree)

1. Enterprise-grade desktop app? → PySide6 (Qt).
2. Mobile or touch-first (Android/iOS) → Kivy (or BeeWare/Toga if you want native, but it’s less mature).
3. Native look is top priority → wxPython.
4. Simple internal tool / teaching → Tkinter or PySimpleGUI.
5. High-FPS, GPU-drawn tools (plots, editors, game tools) → Dear PyGui.
6. You love web UI workflows → pywebview (wraps your Flask/FastAPI app), or Flet.

Packaging & licensing at a glance

• Packaging: PyInstaller works well for Qt, wxPython, Tkinter; Kivy ships its own build tools for mobile; Dear PyGui and PySimpleGUI also package fine.
• Licensing: PySide6 = LGPL (good for closed source). PyQt = GPL/commercial. Others are generally permissive.
• Designer tools: Qt Designer/QML are excellent; others are mostly code-first.

My default recommendation

If you’re building a serious desktop app today and don’t need mobile: PySide6 (Qt) hits the sweet spot for features, stability, docs, and polish with a license that’s friendly to most teams. For quick throwaway tools, Tkinter or PySimpleGUI gets you there fastest. For mobile/touch, Kivy is the most proven Python option.

If you tell me your target OSes, UI complexity, and license needs, I’ll suggest a starter template (and can generate a full skeleton project).