Anthocyanins have a positive effect on resistant obesity; however they cannot usually be absorbed directly but, instead, are metabolized by gut microbiota. This study will examine the effects and the mechanism of vanillic acid on the prevention of obesity induced by diet, which is one of the anthocyanin metabolites. We fed C57BL/6J mice vanillic acid supplements in a high fat and high fructose diet for 16 weeks. Body weight, fat pat weight, and food and water intake were monitored. Glucose homeostasis was assessed with a glucose or insulin tolerance test. The sizes of adipose cells and lipid droplets were analyzed by histology staining, while the expression of genes and proteins was analyzed by quantitative real-time PCR, western blot and tissue-blot immunoassay. The results demonstrated that vanillic acid contributed to the reduction of body weight gain, improved glucose tolerance and insulin resistance, and maintained body temperature. Furthermore, vanillic acid was found to promote thermogenesis and mitochondrial synthesis of brown adipose tissue and inguinal white adipose tissue. This study demonstrated that vanillic acid could prevent obesity by activating BAT thermogenesis and the promotion of inguinal WAT browning.