INTRODUCTION: Chitosan as a natural polysaccharide have been widely applied in biomedicine due to their outstanding biodegradability, non-toxic, and low-price. As carriers, the multi-functional chitosan hydrogels can be prepared by physical and chemical modification to form smart hydrogels to release cargoes. The smart hydrogels can generate sol-gel phase transition while gaining stimulus from the environment including pH, temperature, photo, and so forth. In recent years, a variety of therapeutic approaches such as gene therapy, chemotherapy, and combined therapy can be achieved by combining chitosan-based hydrogels with therapeutic agents. AREAS COVERED: This review reports the state-of-the-art progress of chitosan-based hydrogel delivery systems and some new technologies and discusses the smart chitosan hydrogels. In addition, the current trends and the future prospects together with the drawbacks of chitosan hydrogels as biomaterials are also discussed. EXPERT OPINION: Chitosan as a natural material has been widely studied and reported. Due to its many advantages, the development of chitosan has been applied in all walks of life. However, the application of chitosan hydrogels in disease therapy is limited due to their weak physical and chemical properties in vivo. Thus, it is high likely that chitosan-based hydrogels will contribute to further research and exploration.