The prevalence of adverse effects associated with synthetic pharmaceuticals has underscored the necessity of exploring medicinal plants for the prevention and management of liver pathologies. This study evaluated the hepatoprotective efficacy of the hydroalcoholic extract of Ziziphora clinopodioides in a thioacetamide (TAA)-induced rat model of liver injury. Twenty-five male Wistar rats (250–300 g) were randomly allocated into five groups (n=5 per group): the Negative Control (NC) group (received normal saline), the Positive Control (PC) group (received TAA, 50 mg/kg, intraperitoneally for three consecutive days), and three treatment groups (T1, T2, and T3) that received the TAA-induction protocol followed by daily oral administration of Z. clinopodioides extract at 5, 10, and 20 mg/kg, respectively, for three weeks. Serum levels of alanine transaminase (ALT) and aspartate transaminase (AST) were measured, along with hepatic levels of catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH). Results demonstrated that TAA administration significantly elevated serum ALT and AST activities compared to the NC group (p<0.05). Conversely, oral treatment with Z. clinopodioides extract resulted in a significant reduction in ALT and AST levels, alongside an improvement in antioxidant status (increased CAT, SOD, and GSH, and decreased MDA) compared to the PC group (p<0.05). These findings indicate that the hydroalcoholic extract of Z. clinopodioides exerts a potent hepatoprotective effect against TAA-induced liver damage, likely through its antioxidant constituents.