Objective: Angelica Sinensis Radix (ASR; Dang Gui; the root of Angelica sinensis) is a herbal supplement that has been used in invigorating blood circulation. Here, we provided different lines of evidence to support the beneficial role of ASR against oxidative stress in cultured PC12 cell, a rat pheochromocytoma cell line. Methods: The water extract of ASR inhibited the activity of xanthine oxidase in vitro. In cultures, the pre-treatment of ASR water extract reduced the cytotoxic effect of tert-butyl hydroperoxide (tBHP), an oxidative stress inducer. Results: The protecting mechanisms of ASR were shown to be mediated by: (i) suppression of tBHP-induced reactive oxygen species (ROS) formation; (ii) induction of caspase-3 and PARP activities; and (iii) stimulation of mRNAs encoding antioxidative genes, glutathione S-transferase A2 (GSTA2) and NAD(P)H dehydrogenase quinone oxidoreductase 1 (NQO1), via the transcriptional activation of antioxidant response element (ARE). The outcome was the prevention of tBHP-induced cell apoptosis. Conclusion: Interestingly, the protective effect of ASR extract in PC12 cells were insignificant when challenging by insults of -amlyoid (for Alzheimer’s disease) and MPP+ (for Parkinson’s disease). Taken together, we revealed a neurobeneficial role of ASR in protecting neuronal cells against oxidative damage, which might be useful in developing health food supplements for disease prevention in future.