Abstract: Oyster peptide (OP) has various biological activities. However, its effects on male sexual dysfunction is still poorly understood. In this study, we explored its effects and potential mechanism on male sexual dysfunction. Besides, we established a paroxetine (PRX)-induced sexual dysfunction model by gavaging OP (500 mg·kg^{− 1}) in mice for 28 d. The results show that compared with the model (PRX) group, OP could improve the sexual performance of male mice (P<0.05), restored serum sex hormone levels (P<0.01), increased penile tissue nitric oxide (NO) content (P<0.01), cyclic guanosine monophosphate (cGMP) content (P<0.05) and nitric oxide synthase (NOS) activity (P<0.05), and decreased phosphodiesterase-5 (PDE-5) activity (P<0.01). Meanwhile, OP enhanced testicular marker enzymes activities (P<0.05) and antioxidant capacity (P<0.01), and improved sperm quality. In addition, HE staining results show that OP could restore the number and morphology of spermatogenic cells in seminiferous tubules of mice, and reduced the vacuolization of seminiferous tubules. In conclusion, OP can alleviate PRX-induced sexual dysfunction effectively in male mice and has a potential protective effect on male sexual dysfunction.