Six new depsipeptides, seragamides A–F (1–6), and a known geodiamolide I (7) have been isolated as cytotoxic metabolites from the Okinawan sponge Suberites japonicus. Their structures were elucidated by means of spectroscopic analysis and chemical transformations. Seragamide A (1) promotes the polymerization of G-actin and stabilizes F-actin filaments.