It's often used humorously, but can also have a more serious connotation depending on the context.
Here are some examples of how the idiom is used:
* "He's been acting so strange lately, I think he's lost his marbles." (This implies the person is behaving in a way that is unusual or nonsensical)
* "My grandmother is getting up there in age, she's definitely lost a few marbles." (This refers to senility or dementia)
* "Don't listen to her, she's completely lost her marbles." (This implies the person is not thinking clearly or making illogical decisions)
The origin of the idiom is unclear, but it is believed to have come from the game of marbles, where losing your marbles could mean losing your entire game.