Abstract: As first-line drugs for inhibiting gastric acid and treating digestive system diseases, proton pump inhibitors (PPI) have been found in recent studies to have multi-pathway effects on the regulation of metabolic diseases. There are both therapeutic potentials and risks in the prevention and treatment of metabolic diseases. Studies have indicated that PPI participate in the pathophysiological processes of obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD) through multiple regulatory mechanisms, including reducing levels of appetite-related hormones, improving insulin sensitivity, decreasing hepatic fat accumulation, and modulating fibrotic progression. However, long-term use of PPI has potential risks, including electrolyte disorders, intestinal flora imbalance, osteoporosis, increased risk of fractures, and increased risk of cardiovascular diseases. In clinical application, the medication regimen should be precisely formulated based on the individual characteristics of patients, long-term use without indications should be avoided, and relevant risks should be closely monitored.