Dexlansoprazole, a proton pump inhibitor drug, is utilized for treating erosive esophagitis and non-erosive reflux diseases. In order to investigate the effect of dexlansoprazole on gastric ulcers induced by piroxicam (PXE) in male Albino rats, a study was carried out. A total of fifty adult rats were classified into five groups of ten each. The first group was not given any medication and received only saline, serving as the control. Group 2,3,4 and 5 were received (PXE) 30 mg/ kg b wt. once daily for 3 consecutive days via oral route with second group remained untreated and kept as positive control. The third group of rats were given omeprazole (OMP) 20mg/kg b.wt, fourth group was given dexlansoprazole (DXL) 30mg/b.wt. The fifth group was given DXL 60 mg/b.wt. Groups 3, 4 and 5 were orally administered their drugs once daily for 21 successive days. At the end of the experiment, rats were euthanized and blood samples were collected for determination of serum AST, ALT, ALP, Urea, Creatinine, Uric acid, serum potassium, magnesium, phosphorus and calcium. Stomach was isolated and evaluated for ulcer index, ulcer score and preventive index. A part of the stomach was prepared for tissue homogenate while another part of the stomach and liver was utilized for histopathology. Piroxicam administration resulted in elevation in incidence of gastric ulcer index, and ulcer score, liver function tests and gastric MDA were significantly increased while gastric CAT, SOD and GPx were significantly decreased alongside histopathological alterations were found stomach and hepatic tissues. Treatment with either OMP or DXL elicited significant improvement in the aforementioned parameters.From the obtained results, it could be concluded that both omeprazole and dexlansoprazole are effective medications for treating gastric damage caused by piroxicam, with dexlansoprazole was less superior than omeprazole but with minor adverse events on serum minerals.