Three new cyclohexadepsipeptides, oryzamides A-C (1-3), two isolation artifacts, oryzamides D (4) and E (5), and the known congener scopularide A (6), all possessing a rare 3-hydroxy-4-methyldecanoic acid (HMDA) substructure, were isolated from the mycelial extract of the sponge-derived fungus Nigrospora oryzae PF18. Their planar structures were elucidated by spectroscopic analysis and comparison with the literature data. The absolute configurations were determined using the advanced Marfey's method and single-crystal X-ray diffraction analysis. Among them, oryzamides D (4) and E (5) were a pair of diastereomers at the sulfur atom of the l-methionine sulfoxide residue, which showcased the possible separation of a pair of methionine sulfoxide diastereomers. The X-ray crystal structure of scopularide A (6) was obtained for the first time, thereby establishing its relative and absolute configuration at C-4 of the HMDA residue. Oryzamides A-C (1-3) did not display cytotoxic, antibacterial, antiparasitic, and NF-κB inhibitory activities.