The aim of the study was to investigate the protective effects of vitamin C (Vit C) against the toxic effects of clarithromycin (CLM) administration in rat liver. In the study, rat livers were examined in for liver enzymes, oxidative stress, apoptosis, autophagy, and inflammation. CLM was administered orally at a dose of 45 mg/kg for 7 days. Vitamin C was administered intraperitoneally (i.p.) at 100 mg/kg/day for 7 days. The findings showed that Vit C significantly reduced apoptotic markers, oxidative stress, liver enzymes, autophagic activity, and inflammation in response to CLM administration. In conclusion, the protective effect of Vit C against the toxic effects of CLM, which is widely used in both human and animal health, on the liver has been demonstrated.