Wound healing is a highly sophisticated process, and therefore, a pioneering approach for designing excellent wound dressings with desirable characteristics vital for maintaining the external wound environment by assessing the inherent conditions of a patient for effective wound healing. Silk fibroin (SF), a versatile biocompatible material, has garnered significant attention for its potential in the field of wound healing and tissue regeneration. When SF is blended with polysaccharides, their synergistic properties can result in a material with enhanced bioactivity and tunable mechanical properties that facilitate the controlled release of therapeutic agents. This review explores how SF interacts with certain polysaccharides such as cellulose, chitosan, alginate, and hyaluronic acid (HA) and also delves into the underlying mechanisms through which these SF-polysaccharide blends induce processes such as cell adhesion, proliferation, and differentiation for enhanced wound healing and tissue regeneration. This review also emphasizes the potential of the aforementioned blends in diverse wound healing applications in conjunction with other treatment approaches, further addressing the current challenges in this domain and future directions for optimizing SF-polysaccharide blends for clinical research.