Nanofibers fabricated from various materials such as polymers, carbon, and semiconductors have been widely used for wound healing and tissue engineering applications due to their excellent nontoxic, biocompatible, and biodegradable properties. Nanofibers with a diameter in the nanometer range possess a larger surface area per unit mass permitting easier addition of surface functionalities and release of biotherapeutics incorporated compared with conventional polymeric microfibers. Henceforth, nanofibers are a choice for fabricating scaffolds for the management of wound healing. Nanofibrous scaffolds have emerged as a promising method for fabricating wound dressings since they mimic the fibrous dermal extracellular matrix milieu that offers structural support for wound healing and functional signals for guiding tissue regeneration. Cellulose-based nanofibers have gained significant attention among researchers in the fabrication of on-site biodegradable scaffolds fortified with biotherapeutics in the management of wound healing. Cellulose is a linear, stereoregular insoluble polymer built from repeated units of d-glucopyranose linked with 1,4-β glycoside bonds with a complex and multilevel supramolecular architecture. Cellulose is a choice and has been used by various researchers due to its solubility in many solvents and its capacity for self-assembly into nanofibers, facilitating the mimicry of the natural extracellular matrix fibrous architecture and promoting substantial water retention. It is also abundant and demonstrates low immunogenicity in humans due to its nonanimal origins. To this end, cellulose-based nanofibers have been studied for protein delivery, antibacterial activity, and biosensor applications, among others. Taken together, this review delves into an update on cellulose-based nanofibers fused with bioactive compounds that have not been explored considerably in the past few years.