Polyphenols are the most abundant antioxidants present in the diet and are common constituents of fruits and vegetables. By enhancing the amount of polyphenols ingested through diet, oxidative-stress related diseases such as cardiovascular disease, cancer and other chronic illnesses may be controlled. Three novel varieties of high-polyphenol-containing grapes (V72, V83 & V103) were evaluated for their antioxidant and antiproliferative activities using in-vitro model systems. All the three grape varieties showed high superoxide, hydroxyl, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities. As well, the antioxidant capacity may not be directly correlated with the total polyphenol content. Antiproliferative studies using MCF-7 breast cancer cells revealed that a polyphenol fraction enriched in 3-O-glucosides from all grape varieties inhibited tumor cell growth, with Merlot being the most efficient. Interestingly, a spontaneously immortalized normal cell line MCF-10A did not show any cytotoxic effects even at concentrations where the growth of MCF-7 cells was inhibited by over 80%.