The treatment of ulcerative lesions of the oral mucosa with topical corticosteroids requires special solutions to minimize their systemic toxicity. One strategy to improve the safety profile is the use of oromucosal films based on mucoadhesive biopolymers designed to adhere to the oral mucosa. The composite biopolymer films can also provide prolonged drug release, protect pain receptors, and reduce pain levels. In this study, chitosan-based biocomposite films with the addition of disintegrated bacterial cellulose nanofibers as filler were developed for oromucosal delivery of the high-potency topical corticosteroid clobetasol propionate (CP). The resulting films exhibited good water retention and excellent mechanical properties both in the dry state (Young’s modulus and ultimate deformation were 2.41 GPa and 24%, respectively) and in the swollen state (Young’s modulus was 21.3 MPa and ultimate deformation was 26%). The obtained biocomposite films provided a modified biphasic drug release (60–70% of CP was released within 0.5–1 h; and 100% of CP was released over the following 6 h. In addition, CP incorporated into the biopolymer film retained the ability to suppress the inflammatory response. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2025.