"Be yourself and explain what motivates you," the President said in an exclusive interview with ABC News on Friday.
"I've gotten to know Hillary and seen her work and seen her in tough times and in good times. She is in this for the right reasons. She is motivated by a deep desire to make things better for people," he added.
Clinton and Trump will face off in their first of three presidential debates on September 26 at the Hofstra University on Long Island, New York.
Obama encouraged Clinton to use the debate as a venue to not only talk about policy, but also what has inspired her to carry on in the face of adversity.
"I think there is a reason we haven't had a woman president before and so she is having to break down some barriers," he said.
"There is a level of mistrust and a caricature of her that doesn't jibe with who I know, this person that cares deeply about kids, and wants to make sure they get a good education and wants to make working families have support and wants everyone to succeed and wants to keep America safe."