Regulatory B cells (Bregs) are immune-modulating cells that affect the immune system by producing cytokines or cellular interactions. These cells have immunomodulatory effects on the immune system by cytokine production. The abnormalities in Bregs could be involved in various disorders such as autoimmunity, chronic infectious disease, malignancies, allergies, and primary immunodeficiencies are immune-related scenarios. Ongoing investigation could disclose the biology and the exact phenotype of these cells and also the assigned mechanisms of action of each subset, as a result, potential therapeutic strategies for treating immune-related anomalies. In this review, we collect the findings of human and mouse Bregs and the therapeutic efforts to change the pathogenicity of these cells in diverse disease.