Penicillium genus was a fungal endophyte first reported by Alexander Fleming in 1928 and attracted more attention in recent decades due to its multitudinous metabolites which possess novel skeletons, abundant bioactivities and potential in medicine. Up to now, >300 Penicillium species were found all around the world. The review summarized secondary metabolites derived from the Penicillium genus since 2010, including their chemical structures and biological activities.