The present study evaluated the hepatoprotective properties of Morinda pubescens fruit extract against D-galactosamine (D-GalN)-induced liver injury in rats. The fruit extract of M. pubescens was administrated orally at 200 mg/kg of body weight daily once for 21 days and at 21st day, D-GalN (500 mg/kg of body weight) was injected intraperitoneally in rats, to induce liver damage. In D-GalN administrated rats, significant increase in the levels of serum marker enzymes and lipid peroxidation (LPO) in liver and decreased serum and liver antioxidant levels were observed. Pre-treatment with fruit extract to rats reduced the elevated levels of serum marker enzymes and also improves the levels of fucose, ceruloplasmin, and uric acid. Administration of M. pubescens fruit extract prevented increase of LPO and alteration in iron content in experimental animals, besides, considerably increased the levels of glutathione (GSH) and vitamin E when compared to D-GalN intoxicated animals. The present results suggest that the M. pubescens fruit extract has liver-protective property against D-GalN-induced liver injury in rats, which was further confirmed by histopathological studies. The hepatoprotective potentials of fruits of M. pubescens may be due to the presence of phenols and alkaloids, as analyzed by preliminary phytochemical analysis of fruit extract.