Display omitted •There are many challenges in the treatment of oral lesions, especially cancer.•Controlled release of imiquimod using polymeric films may avoid surgical resection.•The films showed mechanical and adhesion properties compatible with those required for oral use.•The films presented drug release values appropriate for oral use. The immunomodulatory agent imiquimod (IQ) was incorporated in chitosan (Ch) and alginate (A) films aiming at developing a biomaterial to topically treat oral mucosal squamous cell carcinomas. IQ was directly added to either suspensions of the isolated polysaccharides or polyelectrolyte complexes formed by their mixture before film casting. The films presented incorporation efficiencies varying from 55 to 100%, and the highest values were attained for those containing chitosan. The addition of IQ generally increased film opacity and reduced fluid absorption by the films. The drug was released predominantly by diffusion in artificial saliva, resulting in releases of 1.49 to 2.76 μg of drug per mg of film, values considered as appropriate for oral use. Films of different formulations showed no significant differences concerning mucoadhesion properties, and thermogravimetric analysis demonstrated the occurrence of interactions between IQ, Ch, and A. The tensile strength of the films ranged from 16.43 to 64.17 MPa for those without IQ, and from 4.75 to 18.25 MPa for those with the drug, while elongation at break for all dried formulations did not exceed 4%. In conclusion, the films may have high potential as oral cancer therapeutic tools, replacing usual topical gels and creams, which are susceptible to leaching.