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Background: Carbon tetrachloride (CCl₄) is one of the commonly used models for the induction of liver injury and screening of the hepatoprotective activity of different drugs. The aim of this study was to investigate the hepatoprotective activity and possible underlying mechanisms of methanolic and hydroethanolic extracts of Croccus sativus stamens using a model of carbon tetrachloride-induced liver injury in rats. Methods: Methanolic and hydroethanolic extracts was daily orally administered to rats at the doses of 250 mg/kg, prior to double intraperitoneal injection of 1% CCl₄ on 7 days and 14 days. Their activities were compared with silymarin (250 mg/kg) for 14 days. Parameters of hepatic and renal function, lipid profile, and oxidative stress were evaluated in rat serum and tissues. Results: The results indicated that CCl₄ injection in rats increased plasma aspartate aminotransferase (AST), Alanin aminotransferase (ALT), and Alkaline Phosphatase (ALP) activities, which were normalized by methanolic, and hydroethanolic pretreatment. In addition, administration of both extracts with CCl₄ significantly inhibited alterations of kidney indices in the serum levels of creatinine and urea. Moreover, CCl₄ administration increased the lipid peroxidation level (MDA) in tissues that is signifanctly reduced by the Methanolic and hydroethanolic extract of the plant. Methanolic and hydroethanolic treatment improved hepatic antioxidant status, by the elevation of the CAT and GSH level in CCl₄‑administered rats. Conclusion: These findings demonstrated the potential effect of Croccus sativus stamens as a protector against liver injury. Mediated possibly by their antioxidant properties. Which are comparable to those of the standard hepatoprotective compound silymarin.