Triptorelin acetate-loaded poly(lactide-co-glycolide) (PLGA) microspheres have been prepared in binary solvent mixtures composed of dichloromethane (DCM) and acetone (AC). The surface morphology of PLGA microspheres was examined by scanning electron microscopy with varying solvent composition, and the size distribution of PLGA microspheres was measured using a particle size analyzer. Triptorelin acetate is a luteinizing hormone-releasing hormone analog that is used as a model peptide drug. With the increase of AC content in the binary solvent mixture, PLGA microspheres with smooth surface were obtained and this led to an increased loading efficiency with the decreased particle size. For the application of PLGA microspheres as a controlled drug delivery system, the release pattern of triptorelin acetate was observed and the stability of triptorelin acetate-loaded PLGA microspheres was observed with or without mannitol. The sustained release pattern was observed after the initial burst effect and the improved stability of PLGA microspheres was observed with mannitol.