Unavoidable ions in flotation pulp play a critical role in modulating the selective activation or depression of target minerals. This review systematically examines the behavior of Ca²⁺ and Mg²⁺ in mineral flotation. Their primary sources in the pulp are first outlined. Fundamental mechanisms governing their interactions with mineral surfaces are then discussed to establish a theoretical basis for interpreting their flotation behaviors. The activating, depressing, and dispersing effects of these ions on various mineral surfaces are provided, highlighting their multifaceted functions. In addition, strategies to mitigate the adverse impacts of Ca²⁺ and Mg²⁺ are evaluated. This review is intended to guide the optimization of flotation processes, improve the separation efficiency, and provide theoretical and practical insights for mineral processing.