Innate-like B cells (ILBs) are heterogeneous populations of unconventional B cells with innate sensing and responding properties. ILBs in mice are composed of B1 cells, marginal zone (MZ) B cells and other related B cells. ILBs maintain natural IgM levels at steady state, and after innate activation, they can rapidly acquire immune regulatory activities through the secretion of natural IgM and IL-10. Thus, ILBs constitute an important source of IL-10-producing regulatory B cells (Bregs), which have been shown to play critical roles in autoimmunity, inflammation and infection. The present review highlights the latest advances in the field of ILBs and focuses on their regulatory functions. Understanding the regulatory activities of ILBs and their underlying mechanisms could open new avenues in manipulating their functions in inflammatory, infectious and other relevant diseases.