BACKGROUND/OBJECTIVES: A 5:2 intermittent fasting (IF) program is an effective dietary intervention for patients who are overweight or obese, but the effects of a 5:2 IF diet on the Chinese population are unclear. This study examined the impact of a modified 5:2 IF dietary intervention on Chinese adults who were overweight or obese. SUBJECTS/METHODS: In this self-controlled clinical trial, 45 overweight or obese participants received a modified 5:2 IF dietary intervention for 24 weeks. The body weight, body mass index (BMI), waist circumference (WC), glycolipid metabolism indicators, adipokines, and inflammatory factors were measured in all participants at weeks 0 and 24. The changes in body weight and glycolipid metabolism indicators were the primary outcomes. Serum metabolomics analysis was conducted to identify the differences in metabolites and potential metabolic pathways after dietary intervention. RESULTS: Thirty-one participants completed the trial and were included in the final analysis.After 24 weeks of a modified 5:2 IF dietary intervention, the participants showed significant decreases in the BMI, WC, body weight, levels of fasting plasma glucose, fasting plasma insulin, total cholesterol, low-density lipoprotein-cholesterol, interleukin 6, tumor necrosis factor-alpha, alanine aminotransferase, and uric acid (all P < 0.05). Moreover, serum metabolomics analysis identified several significantly altered metabolites and metabolic pathways, including pyruvic acid, alpha-ketoisovaleric acid, ammonia recycling, and glutamate metabolism. CONCLUSION A modified 5:2 IF dietary intervention significantly reduced the body weight in Chinese adults who were overweight or obese.