Obesity has become one of the most prevalent health concerns of our time. A long-term high-fat diet is closely related to obesity. Food emulsifiers are incorporated into high-fat foods to enhance the texture and stability. Whether food emulsifiers exacerbate obesity and metabolic disorders induced by a high-fat diet remains unclear. This study aimed to investigate the effects of polysorbate-80 (P80) and polyglycerol polyricinoleate (PGPR) on lipid metabolism, bile acid profile, and gut microbiota in normal and high-fat-diet-induced obesity in mice. The results of this study showed that P80 and PGPR had little effect on body weight but significantly increased epididymal-fat weight, total energy intake, and blood lipid levels. P80 and PGPR stimulated colon inflammation and improved the expression of inflammatory factors in the colon and liver significantly. P80 and PGPR changed the bile acid profile. However, P80 and PGPR did not aggravate inflammation, obesity and alter bile acid profile by altering the composition of the gut microbiota. The results of this study provide an experimental reference for the rational use of food additives and the adjustment of dietary structure, which are important and have application value.