Metabolic syndrome is a cluster of disorders that increase the risk of cardiovascular disease and diabetes. This study has investigated the responses to rind of yellow mangosteen (Garcinia dulcis), usually discarded as waste, in a rat model of human metabolic syndrome. The rind contains higher concentrations of phytochemicals (such as garcinol, morelloflavone and citric acid) than the pulp. Male Wistar rats aged 8–9 weeks were fed either corn starch diet or high-carbohydrate, high-fat diet for 16 weeks, which were supplemented with 5% freeze-dried G. dulcis fruit rind powder during the last 8 weeks. We characterised metabolic, cardiovascular, liver and gut microbiota parameters. High-carbohydrate, high-fat diet-fed rats developed abdominal obesity, hypertension, increased left ventricular diastolic stiffness, decreased glucose tolerance, fatty liver and reduced Bacteroidia with increased Clostridia in the colonic microbiota. G. dulcis fruit rind powder attenuated these changes, improved cardiovascular and liver structure and function, and attenuated changes in colonic microbiota. G. dulcis fruit rind powder may be effective in metabolic syndrome by appetite suppression, inhibition of inflammatory processes and increased fat metabolism, possibly related to changes in the colonic microbiota. Hence, we propose the use of G. dulcis fruit rind as a functional food to ameliorate symptoms of metabolic syndrome.