The escalating global threat of antimicrobial resistance (AMR) poses a critical public health concern and a significant challenge in modern disease treatment. Chitosan, a naturally occurring polysaccharide, emerges as a promising solution due to its inherent antimicrobial properties, biocompatibility, biodegradability, and environmentally benign nature. Chitosan, due to the presence of cationic amine groups in the molecular backbone, exhibits broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria as well as fungi, gaining significant attention for different biomedical applications. This chapter deals with the recent advancements in the chitosan-based antimicrobial biomaterials as a potential intervention against the recent surge in infectious diseases. It provides a brief overview of the structural parameters dictating the antimicrobial activity of chitosan and detailed chemical modifications performed to enhance its efficacy. Subsequently, the chapter deals with the usage of chitosan and its derivatives to prevent implant-associated infections, such as those in orthopedic implants and catheters, through antimicrobial surface coatings employing both covalent and non-covalent encapsulation of biocides. Additionally, it covers the application of chitosan-based biomaterials in anti-infective wound dressings. Various approaches for incorporating antimicrobial properties into diverse wound healing biomaterials such as hydrogels, sponges, and cryogels through covalent and non-covalent modifications of chitosan and its derivatives are presented. Furthermore, the development of chitosan as therapeutic biomaterials, such as nano and microgels, to cure different systemic infections is discussed. Finally, the chapter concludes with the recent challenges in the clinical application of chitosan-based biomaterials and provides insightful comments to overcome those hurdles.