Imbalanced nutrient intake causes abnormal energy metabolism, which results in obesity. There is feasible evidence that selenium-rich (Se-rich) foods may alleviate obesity and enhance general public health, but the underlying mechanisms remain elusive. Herein we examined the effect of Se supplementation on white adipose tissue beiging process. The mice were fed with a normal diet or a Se-deficient high-fat diet group (DHFD) until there were significant differences in body weight, intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT). Then, the diet of DHFD group was changed to a high-fat diet (HFD) containing specified amounts of selenomethionine (SeMet) (0, 150, 300, and 600 μg/kg) and continued to feed for 14 weeks. Notably, 150 μg/kg SeMet supplement was highly protected from DHFD-induced obesity, insulin resistance, and lipid deposits in liver and kidney, and featured by the enhanced beiging process in white adipose tissue and increased energy expenditure. Moreover, upon cold challenge, 150 μg/kg SeMet supplement enhanced cold tolerance in mice for inducing adipose beiging to promote energy expenditure, evidenced by the increased expression of uncoupling protein-1 (UCP1) in adipocytes. Similarly, SeMet (10 μM) promoted the differentiation of beige adipocytes from the stromal vascular fraction. Collectively, our data support that optimal supplementation of SeMet could enhance the beiging process to attenuate HFD-induced obesity, thus providing new insights into the relationship between dietary SeMet and type 2 diabetes.Copyright © 2022. Published by Elsevier Inc.