Red mud synthetic sand was manufactured by firing and using red mud as the main materials with a small amount of fly ash and bentonite. Alkali activity of red mud synthetic sand was studied by slow alkali-aggregate method. The microzone of interface between red mud synthetic sand and cement was analyzed by SEM-EDS from alkali-aggregate reaction specimen, compared with standard sand and natural fluvial sand specimens. The results show that the expansion rate of specimen is 0.035% in red mud synthetic sand alkali-aggregate reaction on 180 d, which is slightly higher than the expansion rate of specimens in standard sand and natural fluvial sand alkali-aggregate reaction. The expansion rate is less than 0.1% in red mud synthetic sand alkali-aggregate reaction specimen, and meets the requirement as national construction sand. Compared with standard sand and natural fluvial sand in alkali-aggregate reaction specimens, the content of Fe element is highest in the red mud synthetic sand interface on 28 d, and the garnet is generated in the synthetic sand interface. This study can provide a reference for solving accumulation of red mud and shortage of natural sand.