Transient receptor potential melastatin 7 (TRPM7), a member of the TRPM subfamily, is a ubiquitously expressed bifunctional transmembrane protein with a channel domain fused to an active kinase domain. As a non-selective cation channel, TRPM7 is permeable to Ca²⁺, Mg²⁺, Zn²⁺, Na⁺, K⁺, and other trace metals. As an α-kinase, TRPM7 can autophosphorylate its serine and threonine residues, or phosphorylate endogenously targeted substrates such as myosin II. Through the joint action of the two domains, TRPM7 participates in various physiological processes such as Mg²⁺ homeostasis regulation, cell proliferation, differentiation, adhesion and migration, and ultimately affects cell differentiation and embryonic development. Dysfunction of TRPM7 has been associated with multiple neurodegenerative diseases, tissue fibrosis, ischemic injury as well as the occurrence and development of tumors. Genetic or pharmacological deficit of the TRPM7 relieves ischemic neuronal injury and inhibits the proliferation and migration of tumors, while up-regulating or restoring TRPM7 decreases blood pressure, maintains normal embryonic development and may be an effective strategy to treat the neurodegenerative disorders. However, whether TRPM7 is a promising target for the development of clinical drugs remains elusive. Nowadays, several small molecules display activation or inhibitory activities on the TRPM7 channel, and have been successfully used to uncover new cellular roles of TRPM7 in physiological and pathological conditions. Nonetheless, selective and potent TRPM7 modulators are limited. This review summarizes the research progress on the physiological and pathological functions of TRPM7 and its small-molecule modulators, which may provide new therapeutic strategies for TRPM7-related diseases and new directions for the development of novel TRPM7 regulators.