Vitis thunbergii var. taiwaniana (VTT) is a wild grape native to Taiwan, where it has been used as a folk medicine. In this study, we found that the branch and leaf ethanol extracts of VTT significantly inhibited the inducible nitric oxide (NO) synthase protein expression and NO production in BV2 microglia. Using primary neuronal cells, kainic acid (KA) significantly increased hydrogen peroxide production in a dose-dependent manner. All four ethanol extracts of VTT significantly decreased hydrogen peroxide production. However, only root and branch ethanol extracts were able to prevent the neuronal cell death induced by KA in vitro. In the animal study, administration of all four plant part extracts of VTT delayed the onset of seizure and decreased the hippocampus neuronal cell loss, and the neuroprotective activity could be ranked as follows: branch approximately leaf > root > trunk. The results suggest that VTT extracts have a potential to prevent neurodegeneration through the antioxidative activity by their ability to inhibit NO and hydrogen peroxide production.