Erectile dysfunction (ED) is a male sexual disorder mainly caused by a reduction in the cellular concentration of cyclic guanosine monophosphate (cGMP), which is degraded by phosphodiesterase type-5 (PDE-5). Oyster protein (OP) and its hydrolysates have been used for centuries to address male erectile dysfunction, however the mechanisms and evidence supporting their efficacy remain unclear. In this study, OP was hydrolyzed using trypsin to produce peptides that inhibit PDE-5. Following separation by ultrafiltration and Sephadex G-25, a total of 3202 peptides were identified. Virtual screening and molecular docking were employed to identify PDE-5 inhibitory peptides and elucidate their interaction mechanisms with PDE-5. Five peptides with the sequences FLF, LMF, LLW, FGPF, and IPW demonstrated strong interactions with PED5. The results indicated that the key binding sites critical for docking included Phe820, Gln817 and Val782 of the target receptor PED-5. The highest inhibition rate observed for FGPF was 94.6 %, while the inhibition rates for IPW and FLF were 89.0 % and 87.6 %, respectively. The lowest inhibition rate was recorded for LLW at 68 %. These findings suggest that these five peptides have the potential to serve as PDE-5 inhibitors in the health food industry and medicine.