The changes of protein digestibility, the peptides in the digestive juice and angiotensin I converting enzyme (ACE) inhibitory activity after heating of oysters were investigated. The digestibility of raw oysters was 71.1%, and that of oysters heated at 100 °C was 67.9%. A total of 169 and 370 peptides were identified from the digestion of raw oysters and heated oysters, respectively. According to UPLC-Q-TOF-MS spectra, the peptides with a molecular weight below 2000 Da accounted for 87.6% of the total peptides of raw oysters and 94% of heated oysters. Testing the ACE inhibitory activity in vitro, the IC 50 values of raw oyster and cooked oyster were 6.77 lg/mL and 3.34 lg/ mL, respectively. Taken together, the results showed that heated oysters could produce more active peptides and provide ACE inhibitory activity.