Arsenal's form of late has come in for significant criticism, with blame laid at Mustafi's door for goals from Azoye Perez and Shane Long in recent weeks.
However, Wenger insists that his performances are simply down to a lack of confidence, rather than a lack of ability.
"His confidence is lower. He has played many games and most of the mistakes he made have been post-Europa League games because he was a bit jaded," he explained.
"On that front that is part of the fatigue factor which would be the explanation why he had some less good games.
"We are in a job where we can't demand that people, when you make mistakes, say that it's absolutely wonderful. That's part of Arsenal. Like me when I lose games, I have to accept that."
The 25-year-old was linked with a move to Serie A last summer and again in January, but Wenger says a deal was never close.
"He wasn't close [to leaving]. He is a young defender who has had ups and downs. I believe overall he has potential," Wenger insisted. "He is one of the guys who is committed and goes for the challenges.
"He is not one guy who hides from the responsibility, so overall he will be a promising defender for the future. Experience helps.
"In this job, goalkeeper and central defender is a job for old people or older people. So overall that plays a part of course."