Seeds of Hydnocarpus laurifolia (HL) have been used to cure hepatitis by folk medicinal practitioners in the Wayanad hills of Western Ghats of India. The present study was undertaken to evaluate the antioxidant and hepatoprotective activities of the chloroform extract of HL (CHL) using in vitro and in vivo models. The total phenolic and total flavonoid contents of CHL were determined by standard methods. In vitro antioxidant effect of CHL was ascertained by total reduction capability, inhibition of lipid peroxidation and the ability of CHL to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion and hydroxyl free radicals using standard protocols. In vivo antioxidant and hepatoprotective potential of CHL (100 mg/kg; 200 mg/kg) was studied by paracetamol (PCM)-induced hepatotoxicity in Wistar albino rats. CHL exhibited strong in vitro antioxidant activity as demonstrated by the reduction of Fe3+ to Fe2+ (EC50, 320 μg/ml), scavenging of DPPH (IC50, 320 μg/ml), superoxide anion (IC50, 280 μg/ml), hydroxyl (IC50, 290 μg/ml) radicals, and by the inhibition of lipid peroxidation (IC50, 230 μg/ml). CHL was effective in normalizing the serum levels of hepatic enzymes glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase, alkaline phosphatase, total protein, and bilirubin in PCM intoxicated rats. The extract significantly enhanced the levels of hepatic antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione and reduced the thiobarbituric acid reactive substances level in PCM intoxicated rat liver. Histopathological studies of experimental animal liver tissues also confirmed the hepatoprotection exerted by CHL. The observations of this study concluded that CHL possesses significant in vitro and in vivo antioxidant and hepatoprotective effects.