In this work, manganese tailing sand concrete (MTSC) was prepared using manganese tailing sand (MTS) in replacement of river sand (RS) to alleviate the shortage of RS resources and achieve clean treatment and high-value resource utilization of manganese tailing stone. The effects of MTS content on the slump, mechanical strength, air void characteristics, hydration products and micromorphology of MTSC were studied experimentally. The leaching risk of harmful substances in MTSC was also explored by testing the concentration of Mn2+. The results show that the utilization of MTS reduces the slump of MTSC to a certain extent. When the MTS content is lower than 40%, the gypsum introduced by MTS and C3A in cement undergoes a hydration reaction to form ettringite, which decreases the number of pores with a diameter less than 0.1 mm and promotes strength development in MTSC. Additionally, when the MTS content exceeds 40%, the large amount of gypsum reacts to form more ettringite. The expansive stress generated by the ettringite severely damages the pore structure, which is not conducive to the mechanical properties of MTSC. In addition, the leaching of hazardous substances in MTSC is insignificant, and the incorporation of cement can effectively reduce the risk of leaching hazardous substances in MTSC. In summary, it is completely feasible to use MTS to replace RS for concrete preparation when the substitution rate of MTS is less than 40%, with no risk of environmental pollution. The results and adaptation in the concrete industry can reduce the carbon footprint, which is in line with the current trend in civil and materials engineering.