Associations between obesity, diabetes type II, and steatosis have long been recognized. However, a pharmacotherapy that acts in a multifactorial manner controlling the interactions between these conditions is not available. A variety of natural plants, functional fatty acids, and other natural dietary compounds have been used in various anti-obesity products. We investigated the effects of oral administration of an antioxidant carotenoid pigment Bixin and Bixin: β-Cyclodextrin in an obese murine model. C57BL/6 male mice (4–5 weeks) received standard diet (2.18 kcal per 1 g) (CT) and high-fat diet (4.38 kcal per 1 g) (CT/OB, BIX and BIX/βCD) (n = 10 per group). After 16 weeks, the BIX and BIX/βCD were treated by gavage (100 μL day-1) for six weeks, with water (CT and CT/OB groups) and (50 mg kg-1 day-1), Bixin (BIX group) or Bix: β-CD (BIX/βCD). Body weight, Lee's Index, adiposity, CHT, TG, CHT/HDL-c, glucose levels (metabolic markers) and, liver markers (AST and ALT) were determined. All metabolic and liver parameters exhibited down-regulation after oral administration of BIX and BIX/βCD. Particularly relevant was Lee’s Index and adiposity in BIX- and BIX/βCD-treated groups (339.18 g/cm -BIX and 327.58 g/cm -BIX/βCD vs. 360.68 g/cm -CT/OB animals), this finds associated with the insulin sensitivity test, showed a clear association between reduction of adipose tissue and decrease of peripherical insulin resistant. In conclusion, our study suggested that the oral administration of the Bixin and Bix: β-CD inclusion compound improved the metabolic parameters evaluate in obese mice, being more palatable and hepatoprotective.