In recent years, cardiovascular and cerebrovascular diseases have been the focus of several studies. In this study, oyster protein hydrolysate was produced via enzyme hydrolysis and used as a fermentation substrate to ferment recombinant strain PSP2 to produce nattokinase. Using the synergism strategy, fermentation products with fibrinolytic and angiotensin I-converting enzyme (ACE) inhibitory activities were obtained and evaluated. The fermentation medium contained 1.0% trypsin, 1.0% oyster protein hydrolysate, 2.0% maltose, and 0.5% sodium chloride, with an initial pH of 7.0. The maximum nattokinase activity was 390.23 ± 10.24 FU/mL after 72 h of fermentation. The flavor of the product was improved, and heavy metals and volatile salt nitrogen were partially removed via fermentation. The ACE inhibitory activity (IC50) of the fermentation products was 1.433 mg/mL. This study provides a novel approach for the development of marine functional foods with hypotensive and antithrombotic properties.