Transient receptor potential cation channel, subfamily M, member 7 (TRPM7) is a nonselective cation channel permeable to divalent cations including calcium and magnesium. It is C-terminally linked to an a-type serine/threonine protein kinase and is tightly regulated by intracellular and extracellular Mg²⁺. TRPM7 is ubiquitously expressed and has been implicated in pathological conditions like anoxic neuronal death, cardiac fibrosis, metabolic disorders, and tumor cell proliferation. Using a bioluminescence-based assay of TRPM7 channel activity, we performed a high throughput screen for positive and negative modulators of the channel. The identified candidates were further evaluated electrophysiologically by the patch-clamp technique and tested in cell proliferation experiments. We observed that TRPM7 is a target of commonly used activators and inhibitors of SK_Ca channels. We found that the antimalarial plant alkaloid quinine as well as synthetic SK_Ca modulators, such as CyPPA, dequalinium, NS8593, SKA31 and UCL1684, are potent inhibitors of TRPM7. These results indicate that genetically unrelated TRPM7 and SK_Ca channels share a common design of their pore-forming segments. Our findings also highlight the therapeutic potential of drugs targeting SK_Ca channels to be used in pathological conditions involving TRPM7 function.