I'm trying to restore an adult tricycle and the fenders have multiple very small rust holes in them. Can I cut fiberglass cloth and make a "sandwich" with them with the fender in the middle and then cover both sides with resin? Or would a substance like "Bondo" be better?
Both will be workable solutions, provided they are applied correctly, and sealed/painted after.
Do remember that rust is pervasive and never-ending. So you have to de-rust what metal is left properly and not just bog over it.
Also consider that the underside needs to be smooth like the top/visible side too - otherwise water and muck will collect on any protrusion.
If you're not fussed about originality then consider replacing the mudguards/fenders with modern-day plastic ones. They will never rust and will provide a weight saving too.
If the holes are small there is no stress here so any way of filling them is fine. Fiberglass is a good one. You want to clean the fender to make sure the resin will adhere. Bondo would be fine as well. If the holes are very small you may not need to fix them at all unless the appearance bothers you. Any water drop hitting the fender will not have much go through, so the fender will do its job the way it is.