Crocetin is an aglycon of carotenoid extracted by saffron stigmas (Crocus sativus L.) and known to have a potent anti-oxidative effect. Amyliod β (Aβ), hallmark of Alzheimer’s disease, is reported to have neurotoxicity partly via oxidative stress. In this study, we investigated the effect of crocetin on hippocampal HT22 cell death induced by Aβ_1-42. Furthermore, to clarify the mechanism underlying the protective effects of crocetin against Aβ_1-42- induced cell death, we measured reactive oxygen species (ROS) production by CM-H₂DCFDA kit assay. Crocetin at 1 -10 μM protected HT22 cells against Aβ_1-42-induced neuronal cell death and decreased ROS production increased by Aβ_1-42. These results that crocetin has the potent neuroprotective effect against Aβ_1-42-induced cytotoxicity in hippocampal cells by attenuating oxidative stress, suggest that crocetin may provide a useful therapeutic strategy against Aβ-related disorders.