In order to solve the compatibility problem between phosphogypsum-based aggregate and ordinary Portland cement, a core-shell structure phosphogypsum-based aggregate was prepared in this paper. Based on the systematic study of the influence of the composition of aggregate shell on the macroscopic properties such as aggregate water absorption, cylinder compressive strength and compressive strength, the influence of the composition of aggregate shell on the microstructure characteristics of the interfacial transition zone of concrete was studied by means of modern analysis and testing methods. The results show that the performance of the core-shell structure phosphogypsum-based aggregate is improved compared with the uncoated aggregate, and the compressive strength of the concrete test block made of this aggregate and ordinary Portland cement is improved. The interface formed by phosphogypsum-based aggregate and cement with core-shell structure is compared with that without shell. In the early stage of hydration, the content of Ca(OH)2 at the interface is reduced, the pore structure at the interface is optimized, the microhardness at the interface is improved, the width of the interfacial transition zone is reduced, and the shell layer can reduce the probability of S element in the aggregate core diffusing to the interface. In the later stage of hydration, the hydration reaction at the interface is basically stable, and the shell layer can still slow down the trend of S element diffusion from the core to the interface, reduce the risk of expansion and cracking at the interface, and increase the feasibility of the application of phosphogypsum-based aggregate in ordinary Portland cement system.