Chitosan (CS) is the only natural alkaline polysaccharide originated from deacetylation of chitin that is the main component of shell from marine organisms.It has great potential medical application due to its broad-spectrum antimicrobial activity and good water solubility originated from its protonated amino groups under acidic condition and abundant hydroxyl groups.However,unprotonated NH2 group of CS leads to its poor solubility under physiological condition and limits its diverse applications.Therefore,it is highly necessary to summarize the modification strategies of CS derivatives systematically to help researchers select the most appropriate strategies for their specific applications.Herein,we have sum-marized the modification strategies of CS derivatives for improving their antimicrobial activity,water solubility,biocompatibility,and mechanical property by chemical reaction and physical integration.And then we have reviewed the CS derivatives in hydrogels,nanoparticles,or coatings for medical applica-tion in wound dressing,drug delivery,medical implant.Last but not the least,we have put forward the future perspectives of deep studies about structure-activity relationship and clinical applications of CS derivatives.