The protective effects of decursin (D) and decursinol angelate (DA) purified from Angelica gigas Nakai on amyloid β-protein (Aβ)-induced neurotoxicity and the underlying mechanisms were investigated. Aβ plays a major role in the pathogenesis of Alzheimer's disease (AD) by eliciting oxidative stress. It significantly increased cytotoxicity and lipid peroxidation, but decreased glutathione contents and antioxidant enzyme activities. All of these results were markedly reversed by pretreatment with D or DA. Nuclear transcription factor Nrf2, which regulates the expression of antioxidant enzymes, was significantly increased by D or DA pretreatment. Furthermore, D and DA suppressed Aβ aggregation. These results suggest that D and DA increase cellular resistance to Aβ-induced oxidative injury in the rat pheochromocytoma (PC12) cells, presumably through not only the induction of Nrf2 and related antioxidant enzymes, but also the anti-aggregation of Aβ. Thus D and DA have therapeutic potential in treating AD and other oxidative stress-related diseases.