Abstract The peptides inhibiting HIV-1 protease were isolated from the hydrolysate of oyster ( Crassostrea gigas) proteins prepared with thermolysin. The amino acid sequences of the peptides were determined as Leu-Leu-Glu-Tyr-Ser-Ile and Leu-Leu-Glu-Tyr-Ser-Leu. These sequences exist in some proteins of variola major virus or human cytomegalovirus. Chemically synthesized Leu-Leu-Glu-Tyr-Ser-Ile and Leu-Leu-Glu-Tyr-Ser-Leu showed IC 50values of 20 and 15 nM, respectively, and behaved as competitive inhibitors for HIV-1 protease with K i values of 13 and 10 nM, respectively. These peptides were more potent as an HIV-1 protease inhibitor than pepstatin A.