In the present study, we have examined the possible neuroprotective effects of resveratrol and oxyresveratrol against kainic-acid (KA)-induced hippocampal neuronal cell death. Either resveratrol or oxyresvertrol was orally administered 30 min prior to intracerebroventricular (i.c.v.) administration with KA (0.05 μg). Oral pretreatment with oxyresveratrol (50 mg/kg) significantly protected KA-induced hippocampal CA3 neuronal cell death. However, the same dose (50 mg/kg) or a higher dose (100 mg/kg) pretreatment with resveratrol did not affect KA-induced hippocampal neuronal cell death. Furthermore, the i.c.v. pretreatment with 30 μg of oxyresveratrol or resveratrol did not show the protective effect against KA-induced hippocampal neuronal cell death. In the immunohistochemical analysis, FoxO3a and pFoxO3a expressions in the hippocampal CA3 region were significantly increased 30 min after KA administration. Oral pretreatment with oxyresveratrol (50 mg/kg) significantly reduced KA-induced Forkhead homeobox type O3a (FoxO3a) and pFoxO3a expression in CA3 region of the hippocampus, suggesting that oxyresveratrol may exert a neuroprotective effect against KA-induced hippocampal neuronal cell death by reducing the levels of FoxO3a and pFoxO3a protein expression in the hippocampal CA3 region. Furthermore, it is suggested that the neuroprotective effect of orally administered oxyresveratrol against KA-induced neurotoxicity might be possibly mediated by some metabolites rather than direct action of oxyresveratrol on the central nervous system.