Abstract: In this study, TM4 Sertoli cells were injured by triptolide (TP) to construct a germ cell injury model, so as to explore the protective effect of oyster (Crassostrea hongkongensis) hydrolyzed ultrafiltration fractions on TP-induced oxidative damage of TM4 Sertoli cells in mice (Mus musculus). Besides, the molecular mass distribution and trace metal element content of the oyster hydrolyzed ultrafiltration fractions were detected, and the cell viability, GSH content, MDA content and ROS level of TM4 cells induced by TP by ultrafiltration fractions were compared. The results show that the oyster hydrolyzed ultrafiltration fractions are rich in trace metal elements such as copper, zinc, manganese and selenium; most small molecules and macromolecular substances were separated by ultrafiltration; compared with the model group, ultrafiltration fractions improved the cell viability of TM4 cells induced by TP. The cell viability of <3, 3–5 and 5–10 ku ultrafiltration fractions was higher than that of >10 ku ultrafiltration fraction; <3 ku ultrafiltration fraction could prevent TP-induced oxidative stress damage in TM4 cells, reduce the production of intracellular reactive oxygen species and lipid peroxidation, and enhance the antioxidant activity of TM4 cells.