Vitis vinifera leaves are wine industry wastes. In this study, the chemical composition, antioxidant and anti-proliferative activity of six Italian grapevine leaves extracts (Arvino, Gaglioppo, Greco Nero, Magliocco Canino, Magliocco Dolce, and Nocera) were evaluated. HPLC analyses revealed quercetin as dominant constituent (127.52-187.33 mg/kg) followed by rutin (55.99-143.67 mg/kg). The antioxidant activity was determined using DPPH, ABTS, FRAP and β-carotene bleaching tests. Gaglioppo showed the highest radical scavenging ability with IC50 of 7.2 and 19.1 μg/mL, for DPPH and ABTS, respectively. Magliocco Dolce showed a 1.6-times higher FRAP activity than that of the positive control BHT. The anti-proliferative activity was determined by SRB assay against MCF-7, MDA-MB-231, A549 and COR-L23 human tumor cells. Greco Nero showed the highest anti-proliferative activity against MDA-MB-231 with IC50 of 28.4 μg/mL. Based on the obtained results grape leaves should be considered an interesting ingredient for the development of functional food products.