Xanthone compounds have been reported to inhibit cancer cell growth as well as possessing antioxidant properties. The xanthone compound 3-O-demethylswertipunicoside (3-ODS), extracted from Swertia punicea HEMSL, has not previously been demonstrated to have clear neuroprotective effects. In our study, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell death assay revealed that treatment of PC12 cells with 3-ODS ameliorated the decreased cell viability induced by exposure to 1-methyl-4-phenylpyridinium ion (MPP+), rotenone or H2O2. The acridine orange/ethidium bromide (AO/EB) apoptosis assay demonstrated a significant suppression of cell death in PC12 cells. by 3-ODS treatment. 3-ODS increased the protein expression of both tyrosine hydroxylase (TH) and DJ-1 expression in PC12 cells. The current study demonstrates that 3-ODS has potential neuroprotective effects mediated via the elevation of TH and DJ-1 protein levels.