| Summary: | <i>Acrostalagmus</i> is known for its ability to produce numerous bioactive natural products, making it valuable in drug development. This review provides information on the sources, distribution, chemical structure types, biosynthesis, and biological activities of the compounds isolated from the genus <i>Acrostalagmus</i> in the family <i>Plectosphaerellaceae</i> from 1969 to 2022. The results show that 50% of the compounds isolated from <i>Acrostalagmus</i> are new natural products, and 82% of the natural products derived from this genus are from the marine <i>Acrostalagmus</i>. The compounds isolated from <i>Acrostalagmus</i> exhibit diverse structures, with alkaloids being of particular importance, accounting for 56% of the natural products derived from this genus. Furthermore, within the alkaloid class, 61% belong to the epipolythiodioxopiperazine family, highlighting the significance of epipolythiodioxopiperazine as a key characteristic structure within <i>Acrostalagmus</i>. Seventy-two percent of natural products derived from <i>Acrostalagmus</i> display bioactivities, with 50% of the bioactive compounds exhibiting more significant or comparable activities than their positive controls. Interestingly, 89% of potent active compounds are derived from marine fungi, demonstrating their promising potential for development. These findings underscore <i>Acrostalagmus</i>, particularly the marine-derived genus <i>Acrostalagmusas</i>, a valuable source of new bioactive secondary metabolites, and emphasize the vast resource importance of the ocean.
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