An efficient and scalable method to prepare polylactic acid stereocomplex microspheres (sc-PLA-MPs) is achieved. Low molecular weight polylactic acid containing triethoxysilane end-groups (Si-PLA) were firstly synthesized via coupling reaction of 3-(triethoxysilyl)propyl isocyanate with low molecular weight poly (l-lactic acid) (PLLA) and poly (D-lactic acid) (PDLA). Then, the triethoxysilane terminated poly (l-lactic acid) and poly (d-lactic acid) were dissolved in 1,4-dioxane where the triethoxysilane end-groups could hydrolytic condense in-situ, leading to the formation of the architecture having both PLLA and PDLA arms in one molecule, and consequently the stereocomplex microparticles spontaneously precipitated in the form of spherical microspheres with size of approximately ∼5μm.