Cellulose acetate (CA) is a remarkable biomaterial most extensively used in biomedical applications due to their properties. This review highlighted the synthesis and chemical structure of CA polymer as well as focused on the mechanical, chemical, thermal, biocompatible, and biodegradable properties of electrospun CA nanofibers. These properties are essential in the evaluation of the CA nanofibers and provide information as a reference for the further utilization and improvement of CA nanofibers. Moreover, we have summarized the use of electrospun CA nanofibers in the drug delivery system as a carrier for drugs and classify them according to the drug class, including anti-inflammatory, anticancer, antioxidant, antimicrobial agents, vitamins and amino acids. Our review has been concluded that CA nanofibers cannot wholly be biodegraded within the human body due to the absence of cellulase enzyme but degraded by microorganisms. Hence, the biodegradation of CA nanofibers in vivo has addressed as a critical challenge. The preparation of CA began with raw materials and then converted to electrospun nanofibers through electrospinning. Nano-fibres have an extremely high surface-to-volume ratio and high porosity, while some other properties such as thermal, biodegradability, biocompatibility, and tensile strength depend on the type of polymer. Hence, CA nanofibers have great potential in drug delivery applications and have been used to deliver anti-inflammatory, anticancer, antioxidant, antimicrobial agents, as well as vitamins and amino acids. Image 1 • Synthesis of cellulose acetate polymer and its chemical structure. • Physicochemical, mechanical, and biological properties of cellulose acetate nanofibers. • Application of cellulose acetate nanofibers in the drug delivery system. • Cellulose acetate –biodegradation challenge due to absent cellulase enzyme. • Amylose acetate is a suitable carbohydrate polymer to be used in the implantable drug delivery system. [ABSTRACT FROM AUTHOR]