Gastric ulcers (GC) are prevalent gastrointestinal disorders with complex etiologies, including Helicobacter pylori infection and prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs). Curcumin (CUR), with its established anti-inflammatory and antioxidant properties, is limited in clinical application due to poor bioavailability. This study developed oleanolic acid-coated CUR nanoparticles (OC NPs) to enhance the efficacy of CUR in GC prevention. OC NPs were characterized by a spherical shape, demonstrating remarkable improvements in solubility and stability, maintaining structural integrity within biological systems and exhibiting excellent biocompatibility. In vitro studies showed OC NPs reduced inflammation and oxidative stress in GES-1 cells. In vivo, OC NPs effectively prevented ethanol-induced GC in mice by lowering inflammatory cytokines, while increasing antioxidant levels. Histological analysis confirmed enhanced gastric mucosal protection and reduced fibrosis and apoptosis. OC NPs demonstrated prolonged retention in the stomach, offering a targeted drug delivery system. These findings suggested OC NPs as a promising low-toxicity alternative for preventing GC.