Duodenal mucosal resurfacing (DMR) is an innovative endoscopic procedure aimed at treating obesity and type 2 diabetes mellitus (T2DM). This technique modifies the intestinal mucosa, enhances food transit, and regulates the secretion of gastrointestinal hormones, which collectively increases satiety and improves insulin sensitivity. Postoperatively, patients often experience significant weight loss and better glycemic control. This article explores the potential mechanisms by which DMR may alleviate metabolic disorders and evaluates its effectiveness in managing T2DM, obesity, nonalcoholic fatty liver disease (NAFLD), and polycystic ovary syndrome (PCOS).