Heroes forcibly interacting with a Curio will never use a Supply Item, resulting in the default consequences of interacting with the Curio every time regardless of whether this result is innocuous, dangerous, or even deadly. Some afflictions may also cause a forced interaction. For example, a hero with the Necromania quirk may interact with a Dinner Cart or Mummified Remains, both having the 'Body' typing (among others). Specifically, each Curio is associated with a number of 'types', which the conditions respond to. Heroes with certain Quirks or Diseases will sometimes interact with a curio without the player necessarily commanding them to do so this is determined by the type of curio presented and the Hero's condition.

It is advisable, upon activating risky curios, to select a hero with good resistances or one that could potentially be affected by the negative effects without endangering the expedition. The affected hero is always the one currently selected at the moment of activation. Many curios have effects such as stress infliction, healing, bleeding, blighting, the application of buffs and debuffs or granting/removing a Quirk that will affect individual heroes. The Antiquarian can cause special treasure to drop when she interacts with curios. There is a fixed pool of items that is used by specific curios, but additional loot due to low light level will be calculated separately and can be dropped even by curios with very specific loot drops. Normally, the use of the correct provision item will trigger a positive effect, removing the chance of negative effects occurring however, there are a few harmless curios that do not display a prompt and are immediately searched when interacted with. Curios will react differently to certain items. Once the party enters a room or segment with a curio, it can be interacted with to activate a prompt the curio can be investigated directly or with the use of a provision item. Unlike obstacles, curios do not prevent passage if not activated it is thus possible to leave them be to minimize risk, especially if there is a lack of correct provision items to trigger their positive effects. Each room may only contain one curio, while corridor segments can contain more than one. Different locations contain different kinds of curios, but some varieties are found throughout all types of dungeon. Curios can be found inside rooms and corridor segments.

Darkest dungeon laudanum