This behavior pack uses scoreboards to detect if a player has nothing in their mainhand. You can then run your own commands based on the player's score.
Add the Detect Air Add-on to your behavior packs on your world. Behavior packs disable achievements, but editing the world with an NBT editor can re-enable achievements when uploading your world to a realm.
Re-enable achievements on either pc or mobile with the free NBT editor Dovetail
You can give players who are not holding any items in their mainhand an effect, like strength. This example command would be put into a repeating command block, set to unconditional, always active in a tickingarea.
effect @a[scores={detect_air=1}] strength 1 0 true _ _ _ _ _
(_) _ _ | | (_) | | |
____ _ _| |_ _| |_ _____ ____ ___| |_____ _____| | |
| \| (_ _|_ _) ___ | _ \ /___)_____ (____ | | |
| | | | | | |_ | |_| ____| | | |___ | | / ___ | | |
|_|_|_|_| \__) \__)_____)_| |_(___/ |_\_____|\_)_)