Phyllanthus niruri, a well-known medicinal plant, has been widely recognized for its hepatoprotective, anti-inflammatory, and antioxidant properties. In the present study, the hepatoprotective potential of ethanol extract of P. niruri (EPN) and hexane extract of P. niruri (HPN) were evaluated against carbon tetrachloride (CCl₄)-induced hepatotoxicity in rats. Oral administration of both EPN and HPN extracts at the dose of 200 mg/kg body weight and silymarin (50 mg/kg) was assessed for their therapeutic effect on liver function, oxidative stress markers, and inflammatory biomarkers. The results demonstrated that standard drug and P. niruri extracts significantly reduced elevated levels of liver enzymes (ALT and AST), oxidative stress (MDA and NO) markers, and inflammatory markers (TNF-α and TGF-β), along with remarkable restoration of antioxidants (GSH and CAT). Furthermore, histopathological outcomes suggested that the hepatic architecture of liver tissues normalized on extract treatment in comparison to the CCl₄-treated group. The in silico study revealed that 1H-indole, 4-(3-methyl-2-butenyl)- and α-Amyrin from EPN extract, while phenol, 2,4-bis(1,1-dimethylethyl) and Stigmast-4-en-3-one from HPN extract exhibited high binding affinities against selected proteins, TNF-α and TGF-β. These findings highlight P. niruri L. as a valuable source for the development of natural hepatoprotective drugs, as evidenced by its ability to mitigate CCl₄-induced liver toxicity in rats primarily by enhancing antioxidant status and stabilizing liver cell integrity.