Sattahipmycin was isolated from the mycelium of marine-derived <i>Streptomyces</i> sp. GKU 257-1 by following the antibiofilm activity against <i>E. coli</i> NBRC 3972 throughout the purification steps. The structure of sattahipmycin was determined to be a new polycyclic xanthone related to xantholipin but lacking a dioxymethylene and a chlorinated carbon. This compound showed activity toward Gram-positive bacteria and <i>Plasmodium falciparum</i>, antibiofilm formation of <i>Escherichia coli</i>, and cytotoxicity to human cancer cell lines. Using genome sequence data, a biosynthetic pathway leading to sattahipmycin has been proposed involving an uncharacterized type II polyketide synthase biosynthetic gene cluster.