"He's by far the best qualified man, but no. I really don't," she said when asked if the former Florida governor should make a run for the presidency.
"There are a lot of great families, and it's not just four families or whatever," she added. "There are other people out there that are very qualified and we've had enough Bushes."
Her comments on NBC's "Today" show were made from Dallas, where several generations of Bushes had gathered for the dedication of George W. Bush's presidential center.
Jeb's presidential sibling says he wants his brother to run.
"Well, big Jeb, you know, he's got a decision to make," Bush said in an interview aired Wednesday. "And if I could make it for him, it'd be 'run,' but I can't."
Jeb Bush hasn't ruled out the possibility. He said last month, "I'm not going to think about it for 2013."