The prevalence of autoimmune diseases is steadily increasing worldwide. The etiology and pathogenesis of these diseases are extremely complex and largely remain obscure. Meanwhile, a growing body of recent research data points to the critical role of microorganisms in the formation of normal and autoimmune responses in the host organism. One of the leading roles is assigned to the intestinal microbiota represented by trillions of microbes producing a wide range of signaling and immunoregulatory metabolites. Forming a complex interdependent host–microbiota system, symbiotic bacteria largely determine the development and functioning of human immune cells. In this review, we address the role of the intestinal microbiota and its key metabolites (specifically, short-chain fatty acids and tryptophan metabolites) in the pathogenesis of autoimmune disease, and discuss the possible mechanisms of their influence on host immune cells.