Abstract: Acute pancreatitis (AP) is characterized by injury of pancreatic acinar cells, triggering systemic inflammatory response syndrome and multiple organ dysfunction syndrome, and progressing to severe acute pancreatitis (SAP) with significantly increased mortality. As the largest micro-ecosystem in the body, the gut microbiota participates in the digestion and absorption of nutrients and maintains host physiological homeostasis, whilst also playing a pivotal role in inflammatory responses. Dysbiosis of the gut microbiota and AP interact through multiple mechanisms, forming a vicious cycle that promotes disease progression. Modulation of the gut microbiota and restoration of microbial ecological balance can effectively regulate inflammatory cascades, holding promise for reducing the incidence of SAP. This review summarizes the role of the gut microbiota in the disease course of AP and its therapeutic value, aiming to provide new insights into the treatment of acute pancreatitis.