Background: Acetaminophen (APAP) hepatotoxicity is a highly prevalent drug used for the treatment of pain. Allium hooshidaryae is widely used as herbal medicine in western Iran. Objectives: In this study, we investigated the protective effects of A. hooshidaryae methanolic extract (AhME) on liver damage induced by APAP. Methods: Rats were divided into six groups. Groups 1 (negative control) and 2 (positive control) received normal saline; groups 3 received 200 mg/kg of AhME, and groups 4 - 6 received AhME at the doses of 50, 100, and 200 mg/kg once daily, by gavage, respectively. After the 14 days, except for groups 1 and 3, the other groups received 2 g/kg of APAP. After 48 hours, hepatic tissue and blood sample were taken for histopathology and biochemical experiments. Results: APAP induced a notable increase in serum levels of aspartate transaminase (AST, P < 0.001), alanine transaminase (ALT, P < 0.001), alkaline phosphatase (ALP, P < 0.001), lactate dehydrogenase (LDH, P < 0.01), nitric oxide (NO, P < 0.001), and lipid peroxidation (LPO, P < 0.001) levels in hepatic tissue. It also significantly reduced the level of total antioxidant capacity (TAC), total thiol groups (TTGs) as well as glutathione contents (GSH) in hepatic tissue (For all P < 0.001). Following the use of AhME, a noteworthy improvement was observed in hepatic serum enzymes and oxidant/antioxidant parameters in liver tissue. Conclusions: This study demonstrated that AhME prevents APAP-induced hepatotoxicity through improvement in the hepatic antioxidant status.