This study was conducted to measure the antibacterial activity of grape (Vitis vinifera L; Vitaceae) seed extract against methicillin-resistant Staphylococcus aureus (MRSA). Grape seed and skin extracts were tested for antibacterial activity against forty-three strains of MRSA by gel diffusion, growth and respirometric studies. All MRSA strains were found to be sensitive to grape seed extract. Complete inhibition of all bacterial strains tested was observed at a concentration of 3 mg/ml crude grape seed proanthocyanidins extract (GPSE), equivalent of 20.7 µg/ml flavonoid content. Antibacterial activity was bactericidal as shown by a disruption of the bacterial cell wall in scanning and transmission electron microscopy. Grape seed extract is known to be rich in potent antioxidant polyphenolics that could show antibacterial activity. Phenolic compounds in the grape seed extract were assayed by Folin-Ciocalteu’s reagent. The considerable antibacterial activity of commonly available grape seed extract could signify a major advancement in the treatment of MRSA diseases.