Due to the extreme difficulty of cartilage, we endeavored to fabricate a novel biodegradable scaffold using natural polysaccharide cellulose and poly(lactic-co-glycolic acid) (PLGA) microspheres incorporating controllably released the cartilage inducer kartogenin (KGN) for enhancing regenerative healing in cartilage tissue. Initially, to facilitate the loading of KGN, PLGA/KGN microspheres were fabricated using the solvent volatilization method. These microspheres exhibited high sphericity, with particle sizes diminishing from 12.11 to 3.27 μm as the emulsification rate increased. Demonstrating adequate encapsulation efficiency, the microspheres enabled controlled drug release, positively influencing cell migration and recruitment. Subsequently, a biodegradable cellulose composite scaffold loaded with PLGA/KGN microspheres was prepared using the freeze-drying method. Compared with pure MCC scaffolds, composite scaffolds had a lower degradation rate, and the incorporation of microspheres promoted cell proliferation and significantly elevated expression of cartilage-related specific genes. In a rat cartilage defect model, it was further demonstrated that the composite scaffold combined with stem cell implantation achieved an optimal repair effect, characterized by vigorous extracellular matrix secretion and increased maturity of the regenerated cartilage tissues, suggesting potential clinical application value as a novel articular cartilage repair product in the future.