Multiple factors may affect the metabolic fate of carbohydrates. Today, well-standardised and accepted methods may allow for the definitions of the changes in the glucose and insulin curves following the ingestion of either carbohydrate-based and other foods. More debate is still raised on the clinical meaning of these classifications when used at a population level, while emphasis is raised on the approach to carbohydrate metabolism on an individual basis. Within these ranges of applications, other compounds, such as plant polyphenols, may favourably add synergic effects through the modulation of carbohydrate digestion and glucose metabolic steps, resulting in lowering postprandial glucose and insulin levels. Finally, a growing knowledge suggests that the balance of dietary fructose and individual physical activity represent the key point to address the compound towards either positive, energy sparing effects, or a degenerative metabolic burden. The carbohydrate quality within a whole dietary and lifestyle pattern may therefore challenge the individual balance towards health or disease.