Microparticles have a demonstrated value for drug delivery systems. The attempts to develop this technology focus on the generation of featured microparticles for improving the function of the systems. Here, we present a new type of microparticles with gelatin methacrylate (GelMa) cores and poly(L-lactide-co-glycolide) (PLGA) shells for synergistic and sustained drug delivery applications. The microparticles were fabricated by using GelMa aqueous solution and PLGA oil solution as the raw materials of the microfluidic double emulsion templates, in which hydrophilic and hydrophobic actives, such as doxorubicin hydrochloride (DOX, hydrophilic) and camptothecine (CPT, hydrophobic), could be loaded respectively. As the inner cores were polymerized in the microfluidics when the double emulsions were formed, the hydrophilic actives could be trapped in the cores with high efficiency, and the rupture or fusion of the cores could be avoided during the solidification of the microparticle shells with other actives. The size and component of the microparticles can be easily and precisely adjusted by manipulating the flow solutions during the microfluidic emulsification. Because of the solid structure of the resultant microparticles, the encapsulated actives were released from the delivery systems only with the degradation of the biopolymer layers, and thus the burst release of the actives was avoided. These features of the microparticles make them ideal for drug delivery applications.