Oxidative damage has been implicated as one of the leading causes for neuronal cell death in a number of neurodegenerative diseases including stroke. Many vegetables and fruits are enriched in polyphenolic compounds known to exhibit antioxidant properties. This study is to investigate whether dietary supplement with grape powder (GP) may offer protection against neuronal damage due to global cerebral ischemia induced to Mongolian gerbils by occlusion of the common carotid arteries, a model known to cause delayed neuronal death (DND) in the hippocampal CA1 area. Gerbils were fed either a control diet (AIN76a) or a control diet supplemented with low (5.0 g/kg diet) or high (50 g/kg diet) levels of GP for two months. Four days after ischemia/reperfusion (I/R), the extent of DND, glial cell activation, nuclear DNA oxidation, and apoptotic terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labeling (TUNEL) reaction in hippocampal CA1 region were assessed. Ischemia‐induced extensive DND in the CA1 region was accompanied by oxidative and fragmented DNA damage and a marked increase in reactive astrocytes and microglial cells. Dietary GP supplementation significantly protected neurons against I/R‐induced DND, DNA damage, and apoptosis as well as attenuated glial cell activation. These results demonstrate that due to the antioxidant properties of polyphenols in GP, nutritional diets supplemented with grape can protect the brain against ischemic damage. The neuroprotective effects of GP supplement may have wide implication in the future for prevention/protection against other neurodegenerative damage.