The present study was carried out to evaluate the cardioprotective and anti-oxidant activity of methanolic extract of berries of the plant Solanum nigrum belonging to family solanaceae. The cardioprotective activity of the extract was evaluated by using global in-vitro ischemia-reperfusion injury and tissue biochemical anti-oxidant profile respectively. The study was carried out using doses of 2.5 and 5.0 mg/kg for 6 days per week for 30 days. The results indicate that the extract exhibited significant (p<0.001) cardioprotective activity against global in-vitro ischemia-reperfusion injury. The extract also exhibited significant (p<0.001) antioxidant potential as evident from the cardiac tissue biochemical antioxidant profile. Overall, the activities occurred in a dose-independent manner. The present study demonstrated that the methanolic extract of berries of the plant Solanum nigrum possessed cardioprotective and anti-oxidant activity and confirmed the traditional claims.