The formulation and characterization of saxagliptin-loaded gastroretentive microspheres (SMFs) were investigated to enhance drug delivery for sustained therapeutic efficacy. Various formulations (SMF1 to SMF6) were prepared and evaluated for percentage yield, drug entrapment efficiency, buoyancy, floating lag time, particle size, zeta potential, and release kinetics. The percentage yield of SMFs ranged from 67.85% to 73.32%, indicating efficient production processes. Drug entrapment efficiency varied from 65.58% to 75.54%, with SMF4 achieving the highest at 75.54%, suggesting optimal drug loading conditions. SMF4 exhibited a floating lag time of 58±5 seconds and a buoyancy of 78±3%, demonstrating prolonged gastric retention suitable for sustained drug release. Particle size analysis revealed uniformity, supported by SEM images depicting spherical microspheres with smooth surfaces. In vitro release studies over 12 hours showed SMF4 released 99.12% of saxagliptin, following diffusion-controlled mechanisms described by the Higuchi (R² = 0.986) and Korsmeyer-Peppas models (R² = 0.988). The findings underscore SMF4 as a promising gastroretentive system for saxagliptin, offering sustained release properties crucial for managing diabetes mellitus. Further optimization could enhance formulation parameters to refine drug delivery efficiency and therapeutic outcomes.