Alzheimer's disease (AD) is a progressive degenerative brain disorder that is characterized by neuronal loss, neurofibrillary tangles, and the abnormal deposition of senile plaque and amyloid β peptide (Aβ). The brains of AD patients are under intense oxidative stress. The overproduction of Aβ leads to Aβ-associated free radical oxidative stress. In this study, the antioxidative and neuronal protective effects of Punica granatum extract were investigated against oxidative stress-induced cytotoxicity in PC12 cells. The ethanol extracts of P. granatum protected PC12 cells from hydrogen peroxide (H₂O₂-induced oxidative stress. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assays revealed a significant increase in cell viability when oxidatively stressed PC12 cells were treated with the P. granatum extract. To examine the effects of P. granatum on Aβ₁₋₄₂-induced learning and memory impairment in mice, in vivo behavioral tests were performed. Treatment with the extract of P. granatum increased step-through latency in mice injected with Aβ₁₋₄₂. The results of this study suggest that the ethanol extract of P. granatum mitigated H₂O₂-induced oxidative stress in PC12 cells. In addition, the extract inhibited neuronal cell death caused by Aβ-induced oxidative stress and Aβ-induced learning and memory deficiency.