Amoxicillin/ Clavulanate (AC) combination has become one of the antibiotics most widely prescribed used in the treatment of several bacterial infections, associated with liver injury. This study aimed to investigate amoxicillin/clavulanic acid induced hepatotoxicity and the modulatory effect of gallic acid (GA)/ vitamin C (VTC) individually and in combination on oxidative stress-related liver damage. Sixty-four male albino rats were randomly separated into eight groups; negative control; GA group; VTC group; GA +VTC group; AC- treated group; AC + GA- treated group; AC + VTC treated group and AC+ GA + VTC treated group. A twice daily dose of AC (31.83 mg/kg) and a single daily dose of both GA (60 mg/kg) and VTC (200 mg/kg/day) were introduced to rats orally for 7 consecutive days. After sacrificed, blood was collected for biochemical analysis of aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum tumor necrosis factor alpha (TNF-α), caspase-3, RNA of heme oxygenase-1 gene (HMOX-1) and liver sample for lipid peroxidation and histopathological study. The serum levels of AST, ALT and TNF-α were significantly increased and upregulation of caspase-3 protein in rats treated with AC. Hepatic contents of malondialdehyde (MDA) were markedly increased following AC administration but produced a significant decrease in the levels of reduced glutathione (GSH) and glutathione-S-transferase (GST) along with down regulated the expression of HMOX-1. These findings were in accordance with the histopathological findings. Co-administration of GA and/or VTC along with AC to rats reduced liver injury, oxidative stress, apoptosis and histopathological alterations. So, we concluded that GA and VTC pose a positive modulatory effect against AC induced hepatotoxicity