Natural products play a critical role in the promotion of good health as regards the prevention and management of oxidative stress related and neurodegenerative disorders. Oxidative stress has been implicated in several apoptotic pathways associated with cell damages in neuronal disorders. The aim of this study was to investigate the antioxidant effect of trans-N-caffeoyltyramine (TNC) isolated from Cortex lycii against hydrogen peroxide (HO) induced cell damages in PC12 cells as well as its mechanism of action. The results obtained indicated that pretreatment with TNC before the exposure of cells to HO toxicity lead to a significant increase in the cell viability and the antioxidant enzyme activities catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) and reduced the level of malondialdehyde (MDA). Furthermore, TNC attenuated the influx of Ca, ROS formation and restored the impaired mitochondria membrane potential (MMP). Thus TNC may be used as an alternative therapy for the prevention and treatment of neuronal disorders elicited by oxidative stress.