Despite deferasirox (DFX) efficacy in hemochromatosis treatment, it has many gastrointestinal side effects. Omeprazole and other proton pump inhibitors are prescribed for patients complaining from these side effects. Curcumin has anti-inflammatory and antioxidant effects. The study aims to determine the influence of DFX on the histological structure of fundic gastric mucosa of adult male albino rats and to establish the possible beneficial effect of curcumin versus omeprazole. Thirty-two adult male albino rats were split into four groups; control group, group II were treated by DFX (100 mg/kg), group III and group IV received curcumin (100 mg/kg) and omeprazole (20 mg/kg), respectively one hour before administration of DFX. All treatments were given orally once daily for 4 weeks. Samples from the fundus of stomach were subjected to light, immunohistochemical and scanning electron microscopic studies. DFX treated group revealed variable degrees of mucosal lesions by light microscope and were confirmed by scanning electron microscope (SEM). a significant reduction in PAS reaction and a significant increase in cleaved caspase-3 immunohistochemical expression were recorded. The histological structure of fundic mucosa was preserved in both curcumin and omeprazole treated groups, but it was better in curcumin treated group. Curcumin is more effective than omeprazole in preserving changes caused by the administration of DFX on the histological structure of the fundic mucosa of the stomach. So, it is recommended for patients who treated by DFX for long time to protect the gastric mucosa.