Red mud as mine filling materials can solve the storage problems, but metal ions and acid ions in mine water will corrode the filling body and affect their stability. Indoor simulation tests were conducted based on the backgrounds of Bulianta Mine and Cuncaota Mine, and the impact of mine water on the compressive strength of the filling material was characterized by the erosion resistance coefficient to determine the optimal ratio of raw materials. The variation law of compressive strength of the filling body in mine water was analyzed, and the degree of erosion of the filling body by mine water was evaluated through indicators such as compressive strength loss rate and apparent failure path. Combining with testing methods such as scanning electron microscopy and energy dpectrum analysis, the micro mechanism of the action of mine water on the filling body was revealed. The results show that when the mass concentration of the slurry is 56% and the ratio of red mud, calcined kaolin, and cement is 5:4:1, the compressive strength of the specimen at 28 d is 1.98 MPa, and the initial flowability of the slurry is 260 mm, which meets the performance requirements of the filling body and achieves large-scale consumption of red mud. After soaking in sulfuric acid and sodium hydroxide solutions for 28 d, the compressive strength of the specimens decreases by 7.3% and 2.8% respectively compared to pure water immersion conditions, with corresponding corrosion resistance coefficients of 0.92 and 0.97, respectively. The microscopic test results show that the filling body has been in an acid-base environment for a long time, the Si—O—Al bond is broken, and the gel is depolymerized, leading to the gradual reduction of the compressive strength of the filling body. This research can provide a theoretical reference for the engineering application of red mud-based filling materials in mine water.