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Isoniazid (INH) remains a mainstay for TB treatment despite the fact that it can cause liver hepatotoxic. Previous mechanistic hypotheses have classified this type of drug-induced liver injury (DILI) as a metabolic oddity mainly due to bioactivation of the acetylhydrazine metabolites and oxidative stress induced in the liver. Ocimum americanum is an herb from the Lamiaceae family which has phytochemicals that contain antioxidants and have the potential to protect against free radicals and ROS molecules. This study aims to investigate the hepatoprotector potential of ethanol extract of Ocimum americanum L. against INH-induced liver damage in mice. The liver biomarker serum, alanine transaminase (ALT) and aspartate transaminase (AST) were investigated. Treatment groups (INH 100mg/kgBW + OA 2,8 mh/20grBW and INH 100mg/kgBW + OA 5,6 mg/20grBW) were compared to INH group (INH 100 mg/KgBW) and normal control group as well. All treatments were given for 14 days intragastrically. Treatment with INH significantly increased the ALT and AST levels, where OA-treatment reduced these activities in both extract dosage groups (P<0.05). These results suggest that the ethanol extract of Ocimum americanum L. may have antihepatotoxic role related to its antioxidant activity.