Ganoderma lucidum (GL), a traditional Chinese medicinal mushroom, has been widely used for the treatment of chronic hepatopathy of various etiologies. The hepatoprotective activity of peptides from Ganoderma lucidum (GLP) was evaluated against d-galactosamine (d-GalN)-induced hepatic injury in mice. GLP was administered via gavage daily for 2 weeks at doses of 60, 120 and 180 mg/kg, respectively. Control groups were given the same amount of physiological saline synchronously. Then the mice from d-GalN control and GLP-treated groups were treated with d-GalN (750 mg/kg) suspended in normal saline by intraperitoneal injection. d-GalN-induced hepatic damage was manifested by a significant increase in the activities of marker enzymes (AST, ALT) in serum and MDA level in liver (P<0.01), and by a significant decrease in activity of SOD and GSH level in liver (P<0.01). Pretreatment of mice with GLP reversed these altered parameters to normal values. The biochemical results were supplemented by histopathological examination of liver sections. The best hepatoprotective effects of GLP were observed after treatment with the dose of 180 mg/kg as it was evidenced from biochemical parameters and liver histopathological characters which were similar to those of normal control group. Results of this study revealed that GLP could afford a significant protection in the alleviation of d-GalN-induced hepatocellular injury.