There is increasing evidence that microorganisms play a complex and important role in human health and disease, and that the in vivo microbiome can directly or indirectly affect the host’s immune system, endocrine system, and nervous system. Therefore, a relatively stable equilibrium between the host and the microbiome is crucial in human health. However, in the special pathophysiological state of the perioperative period, preoperative anxiety and sleep deprivation, anesthesia intervention and surgical injury, postoperative medication and complications may all have different effects on the microbial composition of various organs in the body, resulting in pathogenic microorganisms, and the balance between beneficial microorganisms is altered. This may affect patient the outcomes and prognosis in a direct or indirect manner. This paper will provide a systematic review of key studies to understand the impact of perioperative stress on the commensal microbiome, provide a fresh perspective on optimizing perioperative management strategies, and discuss possible potential interventions to restore microbiome-mediated steady state.