[Background] Anticancer drug-induced stomatitis develops in 30-40% of cancer patients undergoing chemotherapy. However, medications for this condition are not commercially available in Japan.  [Methods] The oral stomatitis model was prepared by anesthetizing male Golden Syrian hamsters i.p. with 30 mg/kg pentobarbital. The center of the cheek pouch was then exteriorized and sandwiched between ring forceps 5 mm in inside diameter, followed by submucosal injection of 25 µL of 10% acetic acid solution through the ring forceps. Rebamipide nanoparticles were prepared by the wet-milling technique using hydroxypropyl cellulose (HPC-SSL) and sodium dodecyl sulfate. [Results] The results of zeta potential measurement and evaluation of their dispersibility suggested that the prepared nanosuspensions were stable. Furthermore, adhesion of the nanoparticles to the mucous membrane of the oral cavity was evaluated using a quartz crystal microbalance with dissipation monitoring (QCM-D) technology. Application of 3.0 mg/mL rebamipide solution significantly reduced the areas of injury acetic acid-induced oral stomatitis in 5-FU-untreated animals. The application of 3.0 mg/mL rebamipide solution significantly reduced the injured areas of acetic acid-induced oral stomatitis in 5-FU-treated animals. To prevent stomatitis, it appears feasible to utilize RB nanoparticles dispersed in HPC-SSL solution in a mouthwash. [Conclusion] These results suggested that the application of rebamipide reduced the injured areas of an oral stomatitis that developed under chemotherapy-treated conditions.