Background: Mucoadhesive microspheres have emerged as a novel and promising drug delivery approach, gaining significant attention due to their ability to provide controlled and targeted drug release. Objective: This review aims to comprehensively explore recent advancements in the formulation, design, and pharmaceutical__ampersandsignnbsp;applications of mucoadhesive microspheres across multiple routes of administration, including oral, nasal, buccal, ocular, vagi-nal, and rectal. Methods: A systematic analysis of contemporary literature was conducted focusing on formulation strategies, types of polymers, fabrication techniques, and mechanisms of mucoadhesion. Particular attention was given to natural and synthetic polymers such as chitosan, alginate, carbopol, hydroxypropyl methylcellulose, and polycarbophil for their mucoadhesive and sustained-release properties. Recent Advances: Technological innovations in preparation methods__ampersandsignmdash;such as ionotropic gelation, solvent evaporation, spray drying, and coacervation__ampersandsignmdash;have enhanced the physicochemical properties, drug loading efficiency, and bioadhesive strength of microspheres. In addition, the incorporation of novel bioadhesive materials and polymer modifications has enabled the delivery of complex therapeutic agents including peptides, proteins, and vaccines. Applications: Mucoadhesive microspheres offer significant advantages such as enhanced drug absorption, prolonged mucosal residence time, improved therapeutic efficacy, reduced dosing frequency, and minimized systemic side effects. These benefits make them suitable for managing chronic and localized diseases. Conclusion: Mucoadhesive microspheres represent a transformative tool in drug delivery science. This review provides insights into current challenges and future research directions, emphasizing their potential in developing patient-centric, site-specific, and efficient pharmaceutical therapies.