Objectives <p>This RCT aimed to evaluate the effect of topical Rebamipide (regular and nanoparticulated) in comparison to topical Clobetasol propionate in the management of methotrexate-induced oral ulcers in rheumatoid arthritis patients.</p> Materials and methods <p>Patients were divided randomly into three parallel arms: 1% Rebamipide; 1% nanoparticulated Rebamipide, Clobetasol propionate. The outcome measures included WHO oral mucositis grading, pain (NRS), ulcer size, and healing time. The data was analyzed for any statistical significance.</p> Results <p>Intragroup comparisons of mucositis grade improvement and pain reduction revealed significant differences in all the groups. All intergroup comparisons demonstrated non-significant difference, yet nanoparticulated Rebamipide was leading, and all group participants achieved complete healing earlier than the other groups.</p> Conclusion <p>Rebamipide, regular and nanoparticulated forms, showed comparable results to potent Corticosteroid, Clobetasol propionate in management of the oral ulcers.</p> Clinical relevance <p>Rebamipide is an efficient promising alternative modality for management of methotrexate-induced oral ulcers in rheumatoid arthritis patients.</p>