<![CDATA[Chitosan, a natural cationic biopolymer, is gaining popularity in advanced drug delivery systems (DDS) because to its biodegradability and mucoadhesive characteristics. However, its therapeutic efficacy is frequently hampered by weak solubility at physiological pH and inadequate mechanical stability. This paper gives a thorough overview of the most recent advances (up to 2025) in chitosan functionalization to address these constraints. Scientific articles were collected from online database searches on Science Direct, PubMed, and Google Scholar. Chemical modifications such as synthetic and natural cross-linking (e.g., glutaraldehyde, TPP, genipin, vanillin and tannic acid), carboxylation, alkylation, acylation, Quarternization reaction, Graft Copolymerization and the formation of pH-sensitive Schiff bases have made it possible to develop "smart" stimuli-responsive nanocarriers for targeted cancer and gene therapy. Simultaneously, physical approaches like gamma irradiation provide green pathways for producing high-purity, low-molecular-weight chitosan with increased bioactivity. Beyond acting as an inert carrier, modified chitosan demonstrates potent intrinsic antibacterial, antioxidant, anticancer and immunomodulatory activities significantly improving the therapeutic index of encapsulated drugs like paclitaxel and curcumin. This review establishes a roadmap for the clinical translation of multifunctional chitosan derivatives in nanomedicine by bridging the gap between specific modification mechanisms and their biomedical activity.Keywords: Biomedical activity, Characteristic, Chitosan, Modification]]>
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