Aim: Accumulating evidence support a role of polyphenols in the prevention of chronic diseases, i.e. type 2 diabetes (DMT2), cardiovascular diseases and some types of cancer. In the present manuscript, the effect of polyphenol/phenolic compounds on the main cardio-metabolic risk factors (body weight, blood pressure, blood glucose concentrations, plasma lipids, inflammation and oxidative stress) in humans will be discussed. Data synthesis: Epidemiological evidence supports the beneficial effects of polyphenol-rich diets in the prevention of T2D risk. However, the available evidence from the randomized controlled clinical trials did not allow to identify specific phenolic compounds or polyphenol-rich foods that effectively improve cardio-meta...