Oxidative injury has been implicated in the aetiology of Parkinson's disease (PD) and gypenosides (GP), which are saponins with various bioactivities, have shown antioxidative effects in vitro. The present study was designed to evaluate the effect of GP on a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Acute administration of MPTP led to decreased glutathione content and reduced superoxide dismutase activity in the substantia nigra of the mice, which resulted in oxidative stress, loss of nigral dopaminergic neurons and motor dysfunction. Co-treatment with GP attenuated all the injuries induced by MPTP in a dose-dependent manner. The neuroprotective effect of GP may be attributed to increased antioxidation, as manifested by significantly increased glutathione content and enhanced superoxide dismutase activity in the substantia nigra. These results strongly indicate the possible therapeutic potential of GP as an antioxidant in PD.