The antioxidant and hepatoprotective activities of psyllium husk mucilage (PHM) were studied in carbon tetrachloride induced hepatotoxicity rat model. Subsequently, biochemical hepatic parameters were evaluated alongside the assessment of glutathione reductase, superoxide dismutase and catalase potentials in the rats’ liver tissue. Moreover, histopathology and western blot techniques were employed for the assessment of TNF-α protein expression level in the current study. Our results demonstrated that oral administration of PHM at 100 mg/kg in rats significantly ameliorated the deleterious effects induced by CCl4 on the rats’ livers. This was manifested by the substantial results obtained from in vitro antioxidant assays, the reestablishment of the level of different liver biomarkers, the fortification of the liver architecture to close typical and reduction of the TNF-α expression level in comparison to that of CCl4- intoxicated control group. The current approach highlighted the special role of the dietary fiber of psyllium husk, as a promising natural hepatoprotective agent.