Acute pancreatitis (AP) is one of the common digestive system emergencies in clinical practice. Its pathogenesis is complex and has not yet been fully elucidated, and there is also no specific treatment. The finding of creamy ball epidermal growth factor 8 (MFG-E8) has provided a new direction and approach for the diagnosis and treatment of AP. Studies have shown that MFG-E8 is involved in the pathophysiological process of AP and may be the endogenous protection medium of AP. At the same time, the high expression of MFG-E8 in serum of patients with AP may be used as a potential biomarker to evaluate the effectiveness of AP treatment. In recent years, with the deepening of research on the pathophysiological mechanism of AP, calcium-mediated mechanism for acinar cell injury and death has been confirmed, as well as the necessity of eliminating apoptotic and necrotic cells in the AP inflammatory response, and the importance of mitochondrial permeability transition holes and intestinal mucosal barrier in AP. MVG-E8 plays an important role in the occurrence and development of AP. On the one hand, MFG-E8 relieves AP by improving the pancreatic structure, restoring the regeneration function of pancreatic acinar cells and removing the necrotic acinus, and reducing the serum amylase and lipase in AP animal model mice. On the other hand, MFG-E8 promotes macrophage reprogramming through a mediated inflammatory signaling pathway to reduce the production of pro-inflammatory cytokines and thus inhibits AP inflammatory response. At the same time, MFG-E8 can repair the structure and function of mitochondria by improving mitochondrial biogenesis and increasing mitochondrial fusion, thereby reduces oxidative stress response and prevents AP progression. In addition, MFG-E8 also plays an important role in repairing the intestinal mucosal barrier, reducing intestinal bacterial translocation, and improving intestinal ischemia-reperfusion. As a lipophilic anti-inflammatory glycoprotein, MFG-E8 has multiple biological activities against autoimmune and inflammatory diseases, and has multiple biological functions by binding to integrin receptor αvβ3/5 and phosphatidylserine, and is involved in the cellular processes such as maintenance and repair of intestinal epithelial cells, angiogenesis, adhesion and proliferation between tumor cells, and the clearance of apoptotic cells. At present, studies have found that MFG-E8 plays an important role in a variety of diseases, such as infectious diseases, tumors, nervous system diseases, autoimmune diseases. However, the role of MFG-E8 in AP has been recognized only in recent years, and the specific mechanism is still in the preliminary understanding stage and not completely clear. Besides, the current literature reports mostly focus on the inflammatory reaction, mitochondrial function recovery and intestinal mucosal barrier protection, and further research is needed for its role in other pathological mechanisms of AP, such as pancreatic microcirculation. Second, there is no definitive conclusion about the timing, applicable stage and specific dose-effect relationship of MFG-E8 intervention on AP. However, targeting MFG-E8 is a new strategy for the treatment of AP. Therefore, it is important to further study the role of MFG-E8 in the pathogenesis of AP for the diagnosis and treatment of AP. Therefore, in this paper, the structure and function of MFG-E8 and its mechanism of action in AP are reviewed, and the related literature concerning treatment of AP with MFG-E8 as the target is summarized, which will provide a new breakthrough point for the clinical diagnosis and treatment of AP in the future.