The increasing morbidity of oral diseases, such as dental caries, periodontitis and oral cancer, has greatly compromised the life quality of humans. With the rapid development of biomaterials and nanotechnology, various biomaterials-based systems have been reported to treat oral diseases. As the biocompatible, biodegradable and bioadhesive polysaccharide biomaterials, chitosan and its derivatives have also been widely used for the oral disease therapy, either as the antibacterial agents, drug delivery carriers or tissue engineering scaffolds. It has been well demonstrated that chitosan can significantly enhance the therapy efficacy for various oral diseases, due to its intrinsic antibacterial activity and controlled drug release feature. Herein, we aim to provide a comprehensive understanding of the biological functions of chitosan, such as antimicrobial, anticancer and remineralization activity, and summarize the applications of chitosan-based therapeutic systems in treating the typical oral diseases, including dental caries, endodontic diseases, periodontal diseases, oral cancer, oral and maxillofacial surgery, and oral mucosal diseases. In addition, the concerns and possible solutions of the clinical use of chitosan are also discussed.Copyright © 2022 Elsevier B.V. All rights reserved.