The present study evaluated the ameliorative potential of hydroalcoholic extract of Trichosanthes dioica root (TDA) against arsenic induced toxicity in male albino rats. TDA (5 and 10mg/kg) was administered orally to rats for 20 consecutive days before oral administration of sodium arsenite (10mg/kg) for 8 days. Then the body weights, organ weights, haematological profiles, serum biochemical profile; hepatic and renal antioxidative parameters viz. lipid peroxidation, reduced and oxidized glutathione, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase and DNA fragmentation were evaluated. Pretreatment with TDA markedly and significantly normalized body weights, organ weights, haematological profiles, serum biochemical profile and significantly modulated all the hepatic and renal biochemical parameters and reduced DNA fragmentation in arsenic intoxicated rats. The present findings conclude that T. dioica root possessed remarkable ameliorative effect against arsenic induced organ toxicity in male albino rats mediated by alleviation of arsenic induced oxidative stress by multiple mechanisms.