Toluene is extensively used in various industrial processes, and an increasing number of workers are getting exposed to its vapor. Cardiac abnormalities that have been reported in association with toluene exposure are atrioventricular conduction abnormalities, sinus bradycardia, ventricular tachycardia, and coronary vasospasm, therefore, the present study entails the potential cardio protective effects of antioxidants; alpha lipoic acid (ALA) and L-Carnitine (LC) against chronic cardiotoxicity induced by toluene for one month in male rats. Toluene was administered for one month to male Sprague dawely rats. ALA (50 and 100 mg/kg i.p.) and LC (150 mg/kg and 300 mg/kg i.p.) were administered during the last 15 days of treatment. Antioxidants treatment induced a significant therapeutic effect against toluene-induced myocardial damage, which was characterized by increased levels of cardiotoxicity markers: Creatine Kinase iso enzyme-MB (CK-MB) and Lactate dehydrogenase (LDH). As indicators of oxidative stress, toluene caused significant glutathione depletion, elevated lipid peroxidation and reduction in the activities of antioxidant enzymes; glutathione peroxidase (GPx) and glutathione reductase (GR). ALA and LC treatment significantly attenuated toluene mediated-cardiac damage as well as oxidative damage, with LC being more effective than ALA. Furthermore, toluene induced apoptotic cardiac damage as evidenced by increased caspase-3 and caspase-12 activities. ALA and LC treatment attenuated these apoptotic actions of toluene. In addition, toluene increased calpain-2 activity, while ALA and LC ameliorated this effect. Collectively, these findings indicate that ALA and LC possess a potent therapeutic effect against toluene-induced cardiotoxicty effect via suppressing oxidative stress, apoptotic tissue damage and calpain-2 activity.