Asklemmy

It would have to be well hidden or well guarded. Indiana Jones and Tomb Raider come to mind as well.

As many potential rooms as possible in as many locations as possible, and no way to distinguish the right one. Of course, rotate it regularly.

Some old palaces in Japan have "nightingale" floors that purposely squeak to keep people from sneaking in. Could be a security feature outside your room

Is it on display in the bottom drawer of a locked filing cabinet stuck in a disused lavatory with a sign on the door saying, "Beware of the leopard"?

More seriously, just make it an incredibly uninteresting door that no one even thinks about, which everyone thinks is like for plumbing or linens or something boring and irrelevant. Then paint the door in whatever Disney NoSeeUm color is most appropriate.

You can use the low-tech mythos ideology or superstition to keep people out

"We dont go in there because our forebearers spoke of misery to those that enter the room"

The room is built on the inside of a giant snail's shell, if you give it a special kind of lettuce the snail will retreat and clear access to the room.

The whole thing is underwater

Simply put: it stinks, like bad. The room is hidden under the largest city in the land, only accessible by spelunking through vast distances of underground sewers that smell like decomposing waste. This smell-field ensures only the bravest and most dedicated adventurers ever travel to the room, and none who attempt it enjoy talking about it.

Magic can McGuffin any answer you need but it sounds like you want a non magic means to keep people away.

Have a guarded door, be it creature or armed guards. The room that is guarded is not the real room, just a place to hold private meetings. It's used on the regular to keep the focus on the guarded room.

The real room is in the town's bizarre. It's passed by all of the time and is curated by the most hated man. No one likes going to his shop. He's rude and his wares are over priced. Within his shop is the real room that is visited by the few who know.

Boobytraps. Rumours about a curse/ghosts/entry fee. Pretend there's something boring in there. Allow entry, but make the process the full force of German bureaucracy (you need to file form A on a blood moon, to get form A, you need document B2, no not that one the green one, you can get it from Location C but that's only open once a month for half an hour, and if you don't wear pink they won't help you).

Depends on the context, like what world it is and where the room is located, and so on.

I suppose it's in a building that people have access to except for that one room, and that it's a world where, while not particularly sophisticated, explosives exist, so it should at least have very strong walls. If magic exists you might want to avoid using it for this purpose as it often becomes a "because" kind of explaination, but you can use it as a tool (e.g. an obstacle that can only be overcome with powerful magic, and the magicians who are capable of such power can be counted on one hand).

If magic is a no-go, maybe it simply requires a specific kind of key to open (but maybe it's too high tech for your world?)

Put the room in an isolated location? In a cave, on a mountain, hundreds of leagues from the nearest settlement.

Not build a door or windows.

Put a sign "staff only" on the door

Look at ancient Egypt. Big piramides didn't work. Getting your name erased from the society (Tutankhamun) somewhat.

Where is the room exactly? In a house? Palace? What now?

Hiding in plain sight is usually the best way to go about hiding (ime).

But plenty of people know about it...hmm

The room could just be closed off and unaccesible and unnoticeable at the same time..like a hobbit hole with no doors etc.

I'd love more context tbh....and do you write books often?

• Strong locks on doors and windows.
• Reinforce doors and windows with bars or metal.
• Create hidden entrances or passages.
• Use guard dogs to deter intruders.
• Keep heavy furniture near entrances as barricades.
• Set up alarms or noise-making devices.
• Assign a guard or sentry to watch over the room.
• Use traps like tripwires or pitfalls.
• Conceal valuable items or use secret compartments.
• Explore spells or enchantments for added security.

Guards with dogs. Cheaper than most alternatives, covers more ground, harder to confound, works against invisibility and disguises.

The room is filled with a deadly gas. Either it is built so that it vents into the room naturally from deep under ground, or a diffuser is periodically refilled by whoever controls access to the room.

The McGuffin is the antidote to the gas, which you must obtain and administer before entering.

Magic force field ? Or some gaz or magic that disable, give pain or kill when aproaching or entering it, without anybody knowing particularly that "a gaz" is the problem; just that whoever enters get sicks as hell and cannot move anymore

(If want to have a reason why nobody never entered, but your players needs to be able to enter)

Is it on display in the bottom drawer of a locked filing cabinet stuck in a disused lavatory with a sign on the door saying, "Beware of the leopard"?

Smoke and mirrors. Optical illusions. Puzzles. Riddles. Trap doors. Hidden sharp objects. Hidden blunt objects. Needing multiple people to complete something or turning multiple keys or keylike objects from other parts of the story perhaps?

Have you thought of a… lock?

Pit.

You can spread powder on the floor so you could see if someone had stepped in. It wouldn't keep them out unless they didn't want anyone to know they'd been in there.

What does the room contain? If it's a valuable artifact, surround the room with rooms with mundane objects, and build the room around the valuable artifact without any doors or windows.

If the room contains some kind of social circle or government function (think the 5 elder stars in One Piece), I think you'd again try to make the room seem unremarkable, but this time post a guard INSIDE the door. Possibly with an antechamber between the actual room and the hallway so that it seems like there's just a guard in an empty room. Maybe you post many guards there and make it look like its their off duty room where they just hang out