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Grape seed extract (GSE) is a natural product obtained from Vitis vinifera seeds; it has been used as adjuvant therapy in wide range of pathological conditions. In the present study, we investigated the ability of GSE to improve the mental status on ovariectomized rats. GSE (10 mg/kg/day, 60 days long) was administrated orally on ovariectomized adult female rats; then the animals were investigated in open field. Additionally, were measured the hematological parameters, the plasma biochemistry, and the oxidative stress markers. Treatment of GSE improved the loco motor activity in the open field, the number of crossings were almost twice in GSE treated rats (22.25±8.75) compared to placebo group (13.00±2.62)(p< 0.05). Lipid peroxides were reduced up to 51.57%(p< 0.05), while hematology and plasma biochemistry remained almost unchanged. GSE improve the mental status and reduced the level of oxidative stress in rats subject to experimental ovariectomy.