Objective: To study the protective effect of Schisandra chinensis extracts (SCEs) on the RINm5F cells against H2O2-induced oxidative damage and to provide a basis for the study of the role of SCEs in the prevention and treatment of diabetic oxidative stress. Materials and Methods: We performed ultrasonic preparation of SCEs and verified the presence of 8 lignans by high-performance liquid chromatography (HPLC). An in vitro model of H2O2-induced oxidative damage was established using RINm5F cells and treated with various concentrations of SCEs (high dose, medium dose, and low dose). The antioxidative activity of SCEs was observed and its mechanisms were investigated by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay, and measuring malondialdehyde (MDA) and superoxide dismutase assay (SOD) according to the instructions of kits. Results: The total lignan content in SCEs was 18.86 mg/mL; the concentration of 8 kinds of lignans were schisandrin, 5.99 mg/mL; schisandrol B, 3.27 mg/mL; schisantherin A, 1.99 mg/mL; schisanhenol, 0.94 mg/mL; anwulignan, below the detection limit; deoxyschisandrin, 1.33 mg/mL; schisandrin B, 3.95 mg/mL; and schisandrin C, 1.39 mg/mL. SCEs promoted proliferation of islet cells and exhibited a protective effect against H2O2-induced oxidative damage in islet cells. The cell survival rates in the high-dose and medium-dose SCEs groups were greater than that in the model group by 63.4% and 45.6%, respectively; the protective effect of SCEs against oxidative damage was dose dependent. The intracellular MDA content was significantly decreased (P < 0.05), the degree of oxidative damage was reduced, and the activity of superoxide dismutase was significantly increased (P < 0.05) in the SCEs groups. Conclusion: SCEs exhibited a dose-dependent protective effect against H2O2-induced oxidative damage in RINm5F cells. The underlying mechanism was related to the antioxidant activity of the SCEs.