In physiological conditions, a diverse microbiota might enhance host defense. However, the gut microbiota of critically ill patients is characterized by lower diversity, lower abundances of key commensal genera, and overgrowth by one bacterial generation, a state known as dysbiosis. Increasing evidences indicate that microbiota-derived components can reach the systemic circulation from the gut and modulate immune homeostasis. Dysbiosis could have greater consequences for the critically ill patients and might contribute to poor outcome. In this review, we highlighted the crucial role of intestinal microbiota in systemic homeostasis in the critically ill patients and summarized emerging evidence in the field of microbiota-targeted therapies. This would provide new perspective for further establishing the causes and consequences of dysbiosis found in the critically ill patients as well as developing new strategies of intervention.