Chrysosporium, a genus of ascomycete fungi in the family Onygenaceae, has the ability to produce abundant new bioactive natural products, providing a structural foundation in drug development. This review includes the sources, distribution, biological activities and structural characteristics of the compounds isolated from Chrysosporium from 1984 to 2021. The results show that 66% of the compounds isolated from Chrysosporium are new natural products. More than half of the Chrysosporium-isolated compounds are from marine-derived Chrysosporium. The chemical structures of Chrysosporium-derived compounds have different skeletons, which are concentrated in alkaloids, polyketides, and lactones. Eighty percent of the natural products isolated from Chrysosporium have been found to have various biological activities, including cytotoxic, antibacterial, antifungal and enzyme-inhibitory activities. These results demonstrate the potential of Chrysosporium for producing new bioactive secondary metabolites, which can be used as the structural basis for developing new drugs. © 2023 by the authors.