Abstract: Gut microbiota is indispensable for the maintenance of human immune homeostasis. Dysbiosis and translocation of gut microbes as well as aberrance of microbiome metabolites, which are commonly seen in many autoimmune diseases, are suggested to participate in the breakdown of immune tolerance and the excessive inflammatory responses. The involved mechanisms include immune equilibrium skewing, molecular mimicry, bystander activation and epitope spreading, which contributes to the initiation and progression of autoimmune diseases. In addition, the microbial biotransformation of antirheumatic drugs help determine the bioactivity and toxicity of these drugs. Herein, gut microbiota-based intervention may shed light on developing novel strategies for prophylaxis and treatment of autoimmune diseases. In this review, recent advances in exploring the potential pathogenic role of gut microbiota in autoimmunity are summarized and the prospect of applying microbiota-based intervention in systemic autoimmune diseases is addressed.