Coal gangue is a solid waste produced by the coal industry. The continuously produced and long-term stored coal gangue has a certain impact on the environment, so it is urgent to carry out coal gangue resource utilization. The coal gangue in Qianxi city, Guizhou province was used as the research object, coarse coal gangue was used as aggregate, thermal activated fine coal gangue was used as mineral admixture, and the influence of thermal activated coal gangue powder on the properties of matrix-aggregate interface transition zone was studied by compressive and flexural strength testing machine, microhardness meter and scanning electron microscope. The results show that with the increase of thermal activated coal gangue powder amount, both the flexural strength and compressive strength of cement sand test block increase first and then decrease. The thermal activated coal gangue powder with a mass fraction of 2.5% improves the mechanical properties of cement sand test block, reduces the width of interface transition zone, promotes the microhardness of interface transition zone, and compacts the interface structure. With the amount of thermal activated coal gangue powder further increasing, the width of interface transition zone increases, and the number and size of micropore also increase. Some cementing materials are attached to the surface of coal gangue aggregate in clumpy form, which have adverse effects on the mechanical properties of cement sand.