Background: Grapes (Vitis vinifera) are universally appreciated fruit for their delicacy, nutrition and accepted as functional food. The objective of the present study is to evaluate antioxidant and anti-hypercholesterolemic potential of Vitis vinifera leaves extract. Methods: Qualitative and quantitative phytochemical screening of methanolic (VVME) and aqueous (VVAE) extract was carried out to identify the phytoconstituents. Antioxidant potential was evaluated by employing in-vitro and in vivo assays. The anti-hypercholesterolemic activity was evaluated by inducing hypercholesterolemia with high cholesterol diet for 21 days in experimental animals. Results: In VVME, total tannins, total flavonoids and total phenolic contents were found to be present in major amount. Both extract has significant in-vitro and in-vivo antioxidant efficacy. Different doses i.e. 100, 200 and 400 mg/kg of VVME and VVAE significantly attenuated the lipid levels. Moreover, VVME was found to be more effective as compared to VVAE and also, effectiveness was confirmed with histological results. Conclusion: It can be concluded that antioxidant and anti-hypercholesterolemic efficacy of Vitis vinifera might be due to presence of antioxidant property and active phytoconstituents.