Unfortunately, at least I have no definite answer for that. It is always risky to download anything into your computer... However, while using Itch.io, and more precisely the Itch.io App, you can unable itch.io sandbox (Preferences --> Security & privacy) and while it is not perfect and does not actually prevent you from downloading malware, it does at least attempt to minimize the potential harm they can cause.
If someone smarter has a better solution, I'm all ears.