Background: Phyllanthus maderaspatensis species (Euphorbiaceae) has been used in folk medicine of many countries as a remedy against several pathological conditions including jaundice and hepatitis. This study is an attempt to evaluate hepatoprotective activity of P. maderaspatensis against galactosamine-induced toxicity and also investigation of polyphenols in each extract. Materials and Methods: The extraction of P. maderaspatensis as per Ayurveda was simultaneously standardized and quantified for biochemical markers viz., polyphenols: Kaempferol, quercetin, catechin, rutin, and ellagic acid by high-performance thin layer chromatography. Hepatotoxicity was induced albino adult rats by intraperitoneal injection of galactosamine (400 mg/kg). The quantified aqueous, hydroalcoholic and alcoholic extract of P. maderaspatensis (200 and 400 mg/kg body weight/day) were compared for evaluation of hepatoprotective potential, which were assessed in terms of reduction in histological damage, change in serum enzymes such as aspartate amino transaminase, alanine amino transaminase and alkaline phosphatase and increase thiobarbituric acid reactive substances. Results and Discussion: The hydroalcoholic extract was found to contain comparatively high amount of kaempferol, quercetin, catechin, rutin, and ellagic acid which are responsible for hepatoprotection. Antioxidant parameters such as glutathione, catalase, and superoxide dismutase activity in liver tissues were restored toward the normalization more significantly by the hydroalcoholic extract when compared with other extracts. The biochemical observations were supplemented with histopathological examination. Conclusion: The hydroalcoholic extract standardized with respect to known biomarkers may be considered as a potent extract against hepatotoxicity.