Background and aims: Our aims were to investigate changes of bile acids and resting energy expenditure (REE) in patients with type 2 diabetes mellitus (T2DM) after laparoscopic cholecystectomy (LC) and the role in metabolic homeostasis.Methods: From December 2019 to May 2020, a total of 77 T2DM patients with gallbladder polyps were included in our study. Among them, 40 patients who underwent LC were enrolled into cholecystectomy group, 37 patients who did not undergo LC were enrolled into control group. Preoperative and 6-months postoperative demographic data, body weight, food intake, effects on diabetes control, and biomedical variables were recorded and compared.Results: The mean level of total bile acids (TBA) was higher than that in control group (P=0.033) and increased significantly after LC compared to baseline (P=0.029). The resting energy expenditure (REE) level in cholecystectomy group was higher than that in control group (P=0.032) and increased compared to the baseline (P=0.011). The utilization of carbohydrate increased significantly after LC (PP=0.004), A1C (PP=0.045) decreased after LC, as defined, the total effectiveness rate was 45%. The mean level of total cholesterol (P=0.003) and low-density lipoprotein cholesterol significantly decreased (P= 0.021), whereas the level of high-density lipoprotein cholesterol increased (P<0.001). Conclusions: The level of REE and TBA increased after LC in patients with T2DM, the glucose and lipid metabolism improved.Trial registration: Chinese Clinical Trial Registry, ChiCTR1900027823. Registered 30 November 2019, http://www.chictr.org.cn/index.aspx.