I take it you're asking about the safes in the Hearthfire house you have in the works, down in the cellar section.
You don't need a key and nobody will mess with your stuff, whether you store them there, or in containers at the main floor.
You can even store stuff in the chest outside the Hearthfire house. Nobody will touch your stuff. I have left gold and such in there. Perfectly safe. You can always check the UESP wiki for whether certain locations have "safe storage" (all player homes do, except barrels and sacks may respawn). Safe storage basically means "you can put stuff in there and the game won't delete it when the cell resets" - a good example is the College of Winterhold bedroom, where you can defiinitely leave stuff, go away for aaaaaaaages, come back and it's still there (but the cell may well have reset, you can tell by whether the free alchemy ingredients on the little tables have been replenished - NB I have tested this on multiple saves but it's a good idea to test it for yourself before relying on this info).
On the other hand, if you leave stuff in a chest in, say, Faendal's house (once he's your friend and you're able to take stuff without it being stealing) then I believe those containers will reset (also items over a certain value may become marked as 'stolen'.)
I am not aware of NPCs stealing items from chests being possible in the game, although if there's a fight they may grab weapons, usually from racks but possibly from chests, to defend themselves if they are unarmed. They may also take food from tables and whatnot if they have none in their inventory and have an AI package that tells them to eat, I think.
That's why I don't risk storing weapons in the exterior chest. Wouldn't want some bandit group (the ones that randomly spawn to attack the player outside the house) arming themselves with something I wouldn't want them to. Better safe than sorry.
I can't find any hard confirmation, but I'm 90% sure it doesn't happen unless they're unarmed - e.g. if you have two dead bandits, a 'plain' one and an 'outlaw', the plain one only has crappy weapons so you don't loot him, the outlaw has a nice weapon that you want, so you grab it, then realise there's still a third bandit alive, you can raise the plain bandit, who is kinda weak, or the outlaw, who is stronger - if you choose the outlaw, there's a good chance she'll loot the plain bandit's corpse for any weapon she can find. I usually have a bunch of crappy weapons I made for experience and/or a bunch of expensive weapons that I grab a couple of when I'm heading to town to sell stuff, never had any nasty surprises - plus, at Lakeview at least, they usually seem to come from the opposite direction. Still, better safe than sorry, indeed!
I've seen followers grab and use staves -scrolls too. I don't think bandits are different. It would be interesting if I left a staff of paralysis in that chest and waited for the next attack