Amoxicillin/ Clavulanate (AC) combination has become one of the antibiotics most widely prescribed used in the treatment of several bacterial infections, might be associated with liver injury. This study was 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 & 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. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and tumor necrosis factor alpha (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 downregulated the expression of the hemeoxygenase-1 gene (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.