Today’s global food system aggravates climate change while failing in meeting SDG2 and more. Yet, some sustainable food cultures, such as the Mediterranean Diet (MD), are simultaneously safe, healthy, and rooted in biodiversity. Their wide range of fruits, herbs, and vegetables convey many bioactive compounds, often associated with colour, texture, and aroma. Phenolic compounds are largely responsible for such features of MD’s foods. These plant secondary metabolites all share in vitro bioactivities (e.g., antioxidants), and some are evidenced in vivo (e.g., plant sterols lower cholesterol levels in blood). The present work examines the role of polyphenols in the MD, with respect to human and planetary health. Since the commercial interest in polyphenols is increasing, a strategy for the sustainable exploitation of Mediterranean plants is essential in preserving species at risk while valuing local cultivars (e.g., through the geographical indication mechanism). Finally, the linkage of food habits with cultural landscapes, a cornerstone of the MD, should enable awareness-raising about seasonality, endemism, and other natural constraints to ensure the sustainable exploitation of Mediterranean plants.