Abstract: Multiple myeloma (MM) is a malignant proliferative disease of plasma cells in the bone marrow. Despite new drugs significantly improving the prognosis of patients with MM, the problems of relapse and drug resistance remain unsolved. An in-depth understanding of the immune microenvironment of MM may be a potential breakthrough. The formation of an immunosuppressive microenvironment is a prominent feature of MM, which leads to impaired anti-tumor immune surveillance and immune escape of malignant plasma cells. Regulatory immune cells are important factors in the formation of immunosuppressive microenvironment and are closely related to the pathogenesis, progression, and drug resistance of MM. As we enter the era of immunotherapy, the importance of regulatory immune cells in the diagnosis, treatment, and prognosis of MM has been gradually discovered. Changes in their number or proportion may contribute to the early diagnosis and prognostic evaluation of MM. Regulatory immune cells may also become new therapeutic targets. Thus, this review focuses on the research progress of regulatory immune cells in diagnosing and treating MM.