Objective. To evaluate the effect of metformin combined with intensive-exercise diet therapy on glucose and lipid metabolism and islet function in diabetes patients with localized renal cell carcinoma after laparoscopic resection. Methods. A total of 120 renal cancer patients with diabetes mellitus treated in the oncology department of our hospital from January 2018 to December 2020 were recruited and assigned via random number table method at a ratio of 1 : 1 to receive either metformin (control group) or metformin plus intensive exercise diet therapy (study group) after laparoscopic nephrectomy. Outcome measures included glucose and lipid metabolism, pancreatic islet function, lifestyle, clinical efficacy, and adverse reactions. Results. After the intervention, the fasting blood glucose (FBG), 2 h postprandial blood glucose (PBG), glycosylated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) of the two groups of patients decreased significantly, and the study group had significantly lower results. After treatment, the two groups had elevated levels of high-density lipoprotein cholesterol (HDL-C), fasting serum insulin (FINS), and homeostasis model assessment of β-cell function (HOMA-β), and higher results were obtained in the study group (
P
<
0.05
). After the intervention, the study group showed higher results of health promoting lifestyle profile-II (HPLP-II) and a 12-month progression-free survival rate than the control group. There were no significant differences in the incidence of adverse reactions between the two groups. Conclusion. Metformin combined with intensive-exercise diet therapy significantly improves the glucose and lipid metabolism and islet function of renal cancer patients with diabetes and effectively enhances the 12-month progression-free survival. Further trials are, however, required prior to clinical application.