The present study evaluated the ameliorative potential of hydroalcoholic extract of Trichosanthes dioica root (TDA) against arsenic-induced cardiotoxicity in Wistar albino rats. TDA (5 and 10 mg kg-1) was administered orally to rats for 20 consecutive days before oral administration of sodium arsenite (10 mg kg-1) for 8 days. Then the body weights, heart weights, hematological profile, serum biochemical profile; and the following myocardial tissue antioxidative parameters were evaluated: lipid peroxidation, reduced and oxidized glutathione, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, and DNA fragmentation. Pretreatment with TDA markedly and significantly maintained body weights, heart weights, hematological profile, serum biochemical profile. Pretreatment also significantly modulated all of the myocardial antioxidative parameters and reduced DNA fragmentation in arsenic-intoxicated rats. The present findings conclude that T. dioica root possessed remarkable alleviative effect against arsenic-induced myocardial toxicity in Wistar albino rats.