Polylactide (PLA) microspheres have been widely used in various biomedical areas and the performance are greatly determined by the size, morphology and internal structure. Taking advantage of stereocomplex (SC) crystallites formed between poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA), we propose a facile strategy to prepare PLA microspheres with tunable morphology and crystalline structure. Using a solvent evaporation method, a series of PLA microspheres with distinct morphologies (smooth, porous, golf-ball like, guava like) were prepared by changing the proportions of PLLA and PDLA while the size remained almost unchanged. The relationship between morphologies and crystalline structure were analyzed. Both SC crystallites and homocrystallites (HC) existing in the PLLA/PDLA microspheres. With increasing crystallinity of SC-PLA, the microspheres became more porous. To explore the potential applications of PLLA/PDLA microspheres as drug carriers, three typical kinds of Rifampicin-loaded microspheres with different ratio of PLLA and PDLA (10:0, 7:3, 3:7) were prepared and the release test was carried out. Depending on the porosity and crystalline structure, the RFP-loaded microspheres exhibit different release profiles. At 30 h, the cumulative release of 7:3 microspheres could reach 32.6%, which was five times faster than the neat PLLA samples. Our findings not only provide a new strategy to prepare PLA microspheres with controllable morphology but offer additional possibilities for the applications of SC-PLA products in biomedical area.