Mangrove plants grow in tropical and subtropical intertidal zones with acid, salt and oxygen deficit. The particularity of the growth environment provides a special host environment for mangrove fungi. The unique genetic background and metabolic pathway of mangrove-derived fungi make their secondary metabolites have novel structures and diverse biological activities. The genus of Penicillium is widely distributed, which is a large group of mangrove-derived fungi. It can produce metabolites with various structural types and novel structures such as alkaloids, peptides, terpenes, polyketones and other metabolites. Most of them have anti-tumor, anti-inflammatory, anti-bacterial, enzyme inhibitors and other bioactivities. The advances of the 276 natural products produced from mangrove-derived Penicillium in recent 14 years (from 2007 to 2020) are reviewed, in order to provide reference for the development of new natural drugs of mangrove Penicillium sp. fungi.