Systemic lupus erythematosus (SLE) is a chronic, immune-mediated disease associated with significant morbidity and mortality. New evidence suggests that diet, gut microbiota, intestinal permeability, and endotoxemia may modulate chronic inflammation and disease activity in SLE. This review focus on what is known about the gut microbiota in lupus mouse models and SLE patients and the possible mechanisms that connect the gut microbiota with SLE. It included 29 studies (12 animal studies, 15 human studies, and 2 included data on both), with variable results regarding alpha and beta-diversity and gut microbiota composition between lupus-mouse models and SLE patients. Ruminococcus (R.) gnavus was significantly increased in lupus nephritis (LN) in one study, but this was not corroborated by others. Despite the different results, mechanistic lupus mouse model studies have shown that gut microbiota can modulate disease activity. Interestingly, pathobiont translocation in monocolonized and autoimmune-prone mice induced autoantibodies and caused mortality, which could be prevented by a vaccine targeting the pathobiont. Moreover, studies on fecal transplants and diet on different lupus mouse models showed an effect on disease activity. In SLE patients, a higher adherence to the Mediterranean diet was associated with lower disease activity, which may be explained by the connection between diet and gut microbiota. Although gut dysbiosis has been observed in SLE patients and lupus mouse models, it remains to clarify if it is a cause or a consequence of the disease or its treatments. Further studies with larger and well-characterized populations will undoubtedly contribute to deciphering the role of gut microbiota in SLE development, progression, and outcome.