Metabolic syndrome (MetS) is a clinical manifestation characterized by a plethora of comorbidities, including hyperglycemia, abdominal obesity, arterial hypertension, and dyslipidemia. All MetS comorbidities participate to induce a low-grade inflammation state and oxidative stress, typical of this syndrome. MetS is related to an increased risk of cardiovascular diseases and early death, with an important impact on health-care costs. For its clinic management a poly-pharmaceutical therapy is often required, but this can cause side effects and reduce the patient’s compliance. For this reason, finding a valid and alternative therapeutic strategy, natural and free of side effects, could represent a useful tool in the fight the MetS. In this context, the use of functional foods, and the assumption of natural bioactive compounds (NBCs), could exert beneficial effects on body weight, blood pressure and glucose metabolism control, on endothelial damage, on the improvement of lipid profile, on the inflammatory state, and on oxidative stress. This review focuses on the possible beneficial role of NBCs in the prevention and in the clinical management of MetS and its comorbidities.