Gastric ulcer (GU) is a disease characterized by ulcerative lesions on the surface of the stomach mucosa caused mainly by health-related conditions, non-steroidal anti-inflammatory drugs (NSAIDs) use, and Helicobacter pylori infections. The treatment for this disease requires that the drug remains in contact with the site of action, however, the residence time of conventional dosage forms in this organ is limited due to gastric emptying. Curcumin (CUR) is a compound obtained from the rhizomes of the Curcuma longa plant and has been used in traditional Indian medicine for many centuries. However, its use is limited because it has low solubility in aqueous media. In addition, the treatment of gastric diseases requires the drug to remain in contact with the area, but the residence time of conventional dosage forms in this organ is limited. One strategy to overcome these limitations is the use of a gastroretentive and mucoadhesive delivery system. Therefore, this study aimed to develop polymeric chitosan and hydroxypropylmethylcellulose-based microparticles for the release of CUR and to evaluate their in vivo gastroprotective action. The microparticles had a spherical shape and size between 620 and 820 µm, and the encapsulation efficiency was over 50 %, with complete release of CUR after 24 h. Thermal analysis showed changes in the structure of the polymers and CUR, suggesting the establishment of new supramolecular interactions. Microparticles showed high bioadhesive forces to the mucin disc. This set of results, suggest that these systems are promising tools for the prevention of gastric lesions associated with the use of NSAIDs, with a gastroprotective index similar to that conferred by omeprazole.