Our nightstands are open, so we can't hide any ugly/unsightly items (even though that didn't stop us before!).
TOP (my husband's nightstand)
My husband mainly had old books that needed to be put in our bookshelf and/or donated. We sorted through them, and also filed/threw away some old papers that he had there. He still uses the bottom shelf to store his slippers in the wintertime.
BOTTOM (my nightstand)
My nightstand had a lot of photography gear that needed to be stored in another place more accessible and that made more sense (it went into a bin in our backroom closet). I also donated an old clock that I wasn't using, and moved some of the items that I want on my nightstand to the shelf area (lotion, nightguard, TV remote, Kindle).
If we had drawers, I would definitely try to section them off and still keep similar items in them.
The nice part about doing a nightstand is that it's a very small project, even if you have drawers.
Take everything out, clean the surfaces, and sort into trash/keep/donate piles. When you have all the items you want to keep, just take a few moments to think about how you use them/how often, where you need them accessible in/on your nightstand, and if it should be contained (i.e. bins within the drawers).