The aim of present study was to evaluate the antihyperlipidemic effect of grape seeds powder (GSP) and oil (GSO) on lipid profile of hypercholesterolemic rats. The chemical properties of grape seed powder (GSP) and grape seed oil (GSO) were determined. Total phenolic compounds of GSP were determined and fractionated .Results showed that grape seeds are considered to be rich source of natural antioxidants and have bioactive compounds that play a great role to protect human body. Biological evaluation also conducted on hypercholesterolemic rats feed on diets supplemented with GSP and GSO at levels of (4, 5%). The supplementation of GSP and GSO decreased markedly serum TC, TG and LDLC. GSO also significantly reduced liver enzymes levels ALT, AST and ALP, and increased the glutathione content of the liver. The histological examination revealed a potent protective action of GSO rather than GSP, on heart, aorta, and liver. Therefore, use of  GSP (mainly) and GSO as supplements caused significant improvement in biochemical parameters in favor of hypocholesterolemia in all rats groups and could be protect against hypercholesterolemia and can be also used as effective natural antioxidants.