Cardiovascular disorders are the leading cause of death worldwide. Overly high blood cholesterol and oxidative stress are two major risk factors for heart disease. The purpose of this study was to ascertain if grape seed extract (GSE) and lycopene (LCP), two effective antioxidants, could protect against salbutamol's detrimental effects on cardiac functions.In the current study, 42 male albino rats weighing between 150 and 200 grams were divided into six sets of seven rats apiece at random. The experimental groups consisted of the following: (I) control group; (II) salbutamol group, which administered salbutamol (65 mg/kg BW) for two consecutive days in order to induce myocardial toxicity; (III) LCP group, which received LCP (1 mg/kg BW) once daily for three weeks; (IV) GSE group, which received GSE (100 mg/kg BW) once daily for three weeks; (V) LCP preventive group received a three-week pretreatment with LCP once daily for three weeks, followed by two doses of salbutamol; (VI) GSE preventive group received GSE once daily for three weeks before receiving salbutamol for two consecutive days. Every medication was administered orally once a day via gastric tube after being dissolved in regular saline. All rats' groups were examined for serum activity of cardiac enzymes (AST, LDH, CPK, and CK-MB), and serum levels of troponin T (cTnT) and troponin I (cTnI), as well as antioxidant enzymes (CAT, SOD, GPx), and MDA levels in heart tissues. Salbutamol toxicity was found to significantly (P<0.001) raise MDA, troponins, and serum enzyme activity while lowering antioxidant levels. When compared to the salbutamol-induced group, the rats treated with LCP or GSE exhibited a considerable restoration in the activities of antioxidant enzymes and cardiac biomarkers. We conclude that there is significant cardioprotective potential for both LCP and GSE; however, the beneficial effects of GSE are moderately better than LCP.