His father sent him to a woodworking school, but Melki only stayed a few months. At 20 he decided to move towards comedy and took multiple drama classes. Fearful of not being up to par he went to live for several years in Italy.
After a first appearance on screen in 1992 in the Claude Chabrol film Betty, Gilbert Melki rose to prominence in 1996 through Would I Lie To You? by Thomas Gilou in which he played Patrick Abitbol, a great businessman and millionaire megalomaniac, a role he revisited in the sequel in 2001.