Abstract: Autoimmune diseases (ADs) are a kind of local or systemic chronic inflammatory diseases characterized by disorder of the immune system, which seriously affects the quality of life of patients. Clinically, ADs are still incurable, and the main goal of treatment is to reduce disease activity. Inducing the immune system to regenerate antigen-specific immune tolerance and reshape immune homeostasis is the best strategy and ultimate goal for the treatment of ADs. Recently, immunomodulatory nano-preparation based on nanotechnology have shown great potential in inducing antigen-specific immune tolerance. This article reviews the design strategies of immunomodulatory nanopreparation, as well as the latest research progresses of tolerogenic nano-medicine in the treatment of ADs. It also discusses the obstacles facing immunomodulatory nano-preparation in clinical translation, which provides reference for related research on nano-drugs for the treatment of ADs.