The aim of this study was to formulate glipizide loaded PLGA nanoparticles as a sustained release carrier with enhanced efficacy. PLGA nanoparticles (PLGA NPs) were prepared by oil-in-water (o/w) emulsion solvent extraction/evaporation technique with slight modification. The prepared Glipizide NPs demonstrate high drug loading and encapsulation efficiencies. Scanning electron microscope photograph showing spherical and porous morphology of the developed NPs. In-vitro drug release study revealed sustained release of glipizide from the delivery system following the Higuchi (R² = 0.9732) and Ritzer Peppas (R² = 0.9825) model explaining diffusion as well as erosion controlled release. The developed glipizide NPs are suitable for reduction in dosing frequency, decrease in side effects, and improved patient compliance.