Cichorium glandulosum Boiss. et Huet is a native plant used in Traditional Uighur Medicine, especially for treating a variety of liver disorders. In the present study, in vivo hepatoprotective effect of C. glandulosum root extract (CGRE) was evaluated using two experimental models, carbon tetrachloride (CCl4)- and galactosamine (GalN)-induced acute hepatotoxicity in mice. Pretreatment with CGRE (800 mg/kg/day, p.o.) for seven days significantly reduced the impact of CCl4 toxicity (10 mL/kg, i.p.) on the serum markers of liver damage, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). Protective effect was reconfirmed against GalN-induced injury (800 mg/kg b.w., i.p.) and elevated serum enzymatic levels were significantly (p<0.05)and dose dependently restored towards normalization by the extracts. Furthermore, considering the well-known implication of free radicals in tissue injury, in vitro antioxidant properties of the extract were determined with a view to suggest the possible mechanism of activity. The extract showed noticeable antioxidant activity, comparable with standard antioxidants, through its ability to scavenge several free radicals (DPPH, O(2)(-), NO()) and efficiency against lipid peroxidation. Therefore, presented results suggest that CGRE is potent hepatoprotective agent that could protect liver against the acute injury and this ability might be attributed to its antioxidant potential.