Oxidative stress-induced cell damage has been implicated in a variety of neurodegenerative disorders. In the current study, we investigated the protective role of ginsenoside Rd against the cytotoxicity induced by exposure to hydrogen peroxide (H2O2) and the underlying mechanism in the PC12 cell line. The protective effects of ginsenoside Rd (1, 10 μM) on H2O2-induced cytotoxicity may be ascribed to its antioxidative properties by reducing the intracellular reactive oxygen species level; decreasing malondialdehyde production, a common index of lipid peroxidation; and enhancing the antioxidant enzymatic activities of superoxide dismutase and glutathione peroxidase. Additionally, ginsenoside Rd could stabilize the mitochondrial membrane potential after H2O2 exposure. These findings suggested that ginsenoside Rd may be considered a potential antioxidant agent and should encourage further research in neurodegenerative diseases to explore the potential neuroprotective effects of ginsenoside Rd.