An oxidative stress insult is one of the principal causes of Parkinson's disease. Astragaloside IV (AS-IV), a constituent extracted from Astragalus membranaceus, has been demonstrated to exert antioxidant effects. However, the mechanisms responsible for the antioxidant properties and neuro-protective effects of AS-IV remain unclear. In this study, we examined the protective effects of AS-IV against the apoptosis of human neuronal cells (SH-SY5Y cells) induced by hydrogen peroxide (H 2O 2). The results revealed that AS-IV pre-treatment attenuated the H 2O 2-induced loss of SH-SY5Y cells in a dose-dependent manner; AS-IV exerted significant protecitve effects by decreasing the apoptotic ratio and attenuating reactive oxygen species overproduction in H 2O 2-exposed SH-SY5Y cells. By means of immunofluorescence staining, AS-IV was found to decrease the expression of α-synuclein and to increase the expression of tyrosine hydroxylase (TH) in the cells, which had been increased and decreased, respectively by H 2O 2. As shown by western blot analysis, the protective effects of AS-IV against SH-SY5Y cell injury induced by H 2O 2 were also mediated via the downregulation of the ratio of Bax/Bcl-2. We found that the neuroprotective effects of AS-IV were associated with the inhibition of the expression of the α-synuclein via the p38 mitogen-activated protein kinase (MAPK) signalling pathway. On the whole, our results suggest that AS-IV exerts protective effects against neurodegenerative diseases by targeting α-synuclein or TH.