Purpose: To investigate the protective effects of aqueous and methanol extracts of Bidens pilosa using various in vivo and in vitro models of hepatic injury. Methods: One kilogram of the aerial parts of Bidens pilosa was used to prepare 80% methanol and aqueous extracts of the plant (500 g for each extract). The total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity of both extracts were evaluated. The hepatoprotective activity of these extracts in carbon tetrachloride (CCl 4, 0.1%) and D-galactosamine (700 mg/kg)-induced liver injury, respectively, was investigated in mice. Paracetamol-induced liver injury was used as in vitro reference standard. Results: TPC and TFC of methanol extract were higher than those of the aqueous extract. The combination of methanol extract and silymarin showed the highest antioxidant activity. In vivo administration of CCl 4 and D-galactosamine significantly increased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), but decreased the total protein, albumin and glutathione (GSH) contents of liver. Co-administration of the extracts (50 mg/kg) and silymarin (100 mg/kg) effectively countered the effects of CCl 4 and Dgalactosamine, while also exerting their antioxidant properties. Both methanol and aqueous extracts showed hepatoprotective activity in paracetamol-induced cytotoxicity in primary cultures of rat hepatocytes. Conclusion: Bidens pilosa possesses significant in vivo and in vitro hepatoprotective activity in mice and may be therapeutically useful as a protective agent in acute liver injury.