Carbon tetrachloride (CCl₄) is a well-known hepatotoxin that is widely used to induce acute toxic liver injury. Phyllanthus niruri (PN) and Plantago major (PM) have hepatoprotective properties. The purpose of our study was to evaluate the protective effects of PN and PM on CCl₄-intoxicated rats. Sixty male Albino rats were randomly assigned into six equal groups. The first group was kept as a control and received purified water. The second and third groups were administered PN and PM (500 mg/kg/day) orally for 31 days, respectively. The fourth group was injected intraperitoneally with CCl₄ (2 ml/kg/day) on days 15 and 16 of the experiment. The fifth and sixth groups were given PN and PM, and were injected with CCl₄. On days 17 and 32 of the experiment, five rats were assembled randomly from each group, and blood samples were collected for analyzing serum biochemical parameters including liver enzymes, total bilirubin, direct and indirect bilirubin, proteinogram, and lipid profile. Our results revealed a significant increase in ALT, AST, ALP, GGT, total bilirubin, direct and indirect bilirubin, total cholesterol, total triglyceride, LDL-c and VLDL and a significant decline in total protein, albumin, and HDL in the CCl₄ group. However, PN+CCl₄ group significantly improved liver enzymes, bilirubin, albumin, total cholesterol, total triglyceride, LDL-c and VLDL. While the PM+CCl₄ group revealed improvement in AST, ALP, total cholesterol, total triglyceride, LDL-c and VLDL. Finally, it could be concluded that the PN and PM have beneficial effects against CCl₄-induced hepatotoxicity in rats.