Due to the high capacity of impurities in its structure, calcite is regarded as one of the most attractive minerals to trap heavy metals (HMs) and radionuclides via substitution during coprecipitation/crystal growth. As a high-reactivity mineral, calcite may release HMs via dissolution. However, the influence of the incorporated HMs and radionuclides in calcite on its dissolution is unclear. Herein, we reported the dissolution behavior of the synthesized calcite incorporated with cadmium (Cd), cobalt (Co), nickel (Ni), zinc (Zn), and uranium (U). Our findings indicated that the HMs and U in calcite could significantly change the dissolution process of calcite. The results demonstrated that the incorporated HMs and U had both inhibiting and enhancing effects on the solubility of calcite, depending on the type of metals and their content. Furthermore, secondary minerals such as smithsonite (ZnCO3), Co-poor aragonite, and U-rich calcite precipitated during dissolution. Thus, the incorporation of metals into calcite can control the behavior of HMs/uranium, calcite, and even carbon dioxide.