Abstract Regulatory B cells (Bregs) play a crucial role in maintaining immune tolerance and preventing autoimmune diseases. However, in autoimmune conditions, the quantity and function of Bregs are often impaired, leading to pro-inflammatory microenvironment and immune dysregulation. This review provides an in-depth examination of how Bregs are affected in various autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s disease, autoimmune diabetes, and other autoimmune conditions. By summarizing the alterations in Bregs phenotype and function in these specific diseases, we conclude that the Bregs response is complex and variable, showing inconsistent trend across different diseases or even within the same disease. Thus, understanding the heterogeneous nature of Bregs in the autoimmune pathogenesis facilitates novel therapeutic strategies to re-establish immune equilibrium.