Once I actually did it, with a trap that cast Mass Reduce Person in 3e, but other than a minor debuff to the melee it wasn't that big a deal.
I kind of did it in the old Ravenloft adventure, The Created, where the players had their minds put into tiny marionette bodies, which featured a deadly fight with an old tomcat- back when a regular housecat was lethal to 1HD creatures, lol.
I think the easiest way to do it would be to scale up any enemies faced. Regular humans could become ogres or giants, there's plenty of giant regular animals in the Monster Manual and other books. That way you don't have to putter about trying to accurately nerf the PC's by massively reducing Strength scores or increasing damage dealt to them. That is, if fair combats are your aim.
Forcing players to avoid combat with a foe they couldn't possibly fight at a tiny scale through stealth or ingenuity is a perfectly cromulent adventure- think of the old sci fi movie, Dr. Cyclops, where some people reduced to 1/12th scale have to take on a regular sized mad scientist. The trick, I think, would come down to magic. While you could say that spells do less damage or have smaller areas of effect when cast by smaller characters (something not well supported by any edition of D&D, for example, thanks to the myriad of small Fey magic users), that doesn't reduce the utility of magic.
Though you could shrink the characters and not their gear or spell components effectively, but that's just a "you got captured/imprisoned" type scenario by another name. Most characters do not function without equipment, unless you have a party of Monks, lol.