Display omitted •This review focuses on the structural optimization strategy of cationic chitosan.•Antifungal activities and potential applications of cationic chitosan derivatives are described and summarized.•Challenges, shortcomings, and prospect of cationic chitosan derivatives as antifungal therapy are emphasized and commented. The increasing resistance of pathogen fungi poses a global public concern. There are several limitations in current antifungals, including few available fungicides, severe toxicity of some fungicides, and drug resistance. Therefore, there is an urgent need to develop new antifungals with novel targets. Chitosan has been recognized as a potential antifungal substance due to its good biocompatibility, biodegradability, non-toxicity, and availability in abundance, but its applications are hampered by the low charge density results in low solubility at physiological pH. It is believed that enhancing the positive charge density of chitosan may be the most effective approach to improve both its solubility and antifungal activity. Hence, this review mainly focuses on the structural optimization strategy of cationic chitosan and the potential antifungal applications. This review also assesses and comments on the challenges, shortcomings, and prospect of cationic chitosan derivatives as antifungal therapy.