Systematic lupus erythematosus (SLE) is an autoimmune disease reflecting an imbalance between effector and regulatory immune responses. Dendritic cells (DC) are a link between innate and adaptive immunity. Inflammatory DCs (inflDC) can initiate and trigger lymphocyte responses in SLE with over-expression of surface molecules and pro-inflammatory cytokine, including Interferon (IFN) α, Interleukin (IL) 1α, IL-1β, and IL-6, resulting in the overreaction of T helper cells (Th), and B cells immune responses. On the opposite side, tolerogenic DCs (tolDC) express inhibitory interacting surface molecules and repressive mediators, such as IL-10, Transforming growth factor beta (TGF-β), and Indoleamine 2, 3-dioxygenase (IDO), which can maintain self-tolerance in SLE by induction of regulatory T cells (Treg), T cells deletion and anergy. Hence, tolDCs can be a therapeutic candidate for patients with SLE to suppress their systematic inflammation. Recent pre-clinical and clinical studies showed the efficacy of tolDCs therapy in autoimmune diseases. In this review, we provide a wide perspective on the effect of inflDCs in promoting inflammation and the role of tolDC in the suppression of immune cells' overreaction in SLE. Furthermore, we reviewed the finding of clinical trials and experimental studies related to autoimmune diseases, particularly SLE.