Drug delivery systems have revolutionized traditional drug administration methods by addressing various challenges, such as enhancing drug solubility, prolonging effectiveness, minimizing adverse effects, and preserving potency. Nanotechnology-based drug delivery systems, particularly nanoparticles (NPs) and nanofibers (NFs), have emerged as promising solutions for biomedicine delivery. NFs, with their ability to mimic the porous and fibrous structures of biological tissues, have garnered significant interest in drug-delivering applications. Biopolymers such as gelatin (Ge) and chitosan (CH) have gained much more attention due to their biocompatibility, biodegradability, and versatility in biomedical applications. CH exhibits exceptional biocompatibility, anti-bacterial activity, and wound healing capabilities, whereas Ge provides good biocompatibility and cell adhesion properties. Ge/CH-based NFs stimulate cellular connections and facilitate tissue regeneration owing to their structural resemblance to the extracellular matrix. This review explores the additive methods of preparation, including electrospinning, force pinning, and template synthesis, focusing on electrospinning and the factors influencing the fiber structure. The properties of Ge and CH, their role in drug release, formulation strategies, and characterization techniques for electrospun fibers are discussed. Furthermore, this review addresses applications in delivering active moieties in the management of orthopedics and wound healing with regulatory considerations, along with challenges related to them. Thus, the review aims to provide a comprehensive overview of the potential of Ge/CH-based NFs for drug delivery and biomedical applications.