The rapper slated the hip-hop mogul and his new group Diddy-Dirty Money, reports the Daily Mirror.
"Puffy is a bitch. He wanted to be the hot bitch in his group," he said during an appearance on Eminem's radio station Shade 45.
"You know how an ugly bitch surrounds herself with pretty girls? Well, he is the pretty bitch with the other girls around him. He will suck the life out of everyone he is around."
Last month, 50 Cent claimed that Diddy was not a real artist.