| Summary: | Three novel cyclic hexapeptides, sclerotides C–E (<b>1</b>–<b>3</b>), and a new lipodepsipeptide, scopularide I (<b>4</b>), together with a known cyclic hexapeptide sclerotide A (<b>5</b>), were isolated from fermented rice cultures of a soft coral-derived fungus: <i>Aspergillus sclerotiorum</i> SCSIO 41031. The structures of the new peptides were determined by 1D and 2D NMR spectroscopic analysis, Marfey’s method, ESIMS/MS analysis, and single crystal X-ray diffraction analysis. Scopularide I (<b>4</b>) exhibited acetylcholinesterase inhibitory activity with an IC<sub>50</sub> value of 15.6 μM, and weak cytotoxicity against the human nasopharyngeal carcinoma cell line HONE-EBV with IC<sub>50</sub> value of 10.1 μM.
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