Objective: This study was carried to investigate the role of chitosan nanoparticle in protecting against cadmium chloride-induced gastric toxicity in the rat. Methods: The 50 male rats were divided into 5 group: negative control (Rats were given daily with aquadest) ; positive control (Rats were given daily with cadmium chloride 5 mg/kg BW orally once in a day for 28 days) and the treatment group (Rats were given the chitosan nanoparticle 150 mg; 300 mg; 600 mg/kg BW orally once in a day for 32 days and on 4 th day, were given cadmium chloride 5 mg/kg BW one hour after the chitosan nanoparticle administration for 28 days). On day 32, the rats were sacrificed, and gastric tissues were collected to measure Malondialdehyde (MDA), Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx) and histological evaluations. Results: Oral administration of cadmium chloride 5 mg/kg BW for 28 days significant induced gastric mucosal hemorrhagic lesions, increase MDA, decrease SOD and GPx, and also caused necrosis of gastric mucosal epithelial cell in the rat. Treatment with the chitosan nanoparticle 600 mg/kg BW but not 150 mg/kg BW and 300 mg/kg BW significantly improved gastric injury, decreased MDA, increase in SOD and GPx levels, and also improved necrosis of gastric mucosal epithelial cell as compared to positive control group. Conclusion: From the results of this study concluded that the chitosan nanoparticle could be a potent natural product provide a promising gastroprotective effect against cadmium chloride induced gastric toxicity in rats.This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.