The Mediterranean diet (MedDiet) is a plant-based diet characterised by a high consumption of fruits, vegetables, nuts, olive oil, and unrefined grains, which are major sources of polyphenols. Among these, hydroxybenzoic acids are the most abundant phenolic acids, while flavanols, flavonols, flavanones, and anthocyanins are the most prevalent flavonoids in the MedDiet. Polyphenols found in the MedDiet have been shown to influence mitochondrial dysfunction, deregulated nutrient sensing, autophagy, cellular senescence, and dysbiosis through hormesis in cellular and animal models. According to epidemiological studies, dietary intake of total polyphenols is nearly equivalent to that obtained through commercially available polyphenol supplements. However, factors such as the food matrix and bioavailability must be considered within a hormetic model when suggesting intake levels for promoting healthy longevity. While combining dietary and supplemental intake may be a viable alternative, more clinical trials including those incorporating nutrigenetic data are needed to establish evidence-based daily intake recommendations for polyphenols. Longitudinal epidemiological and clinical studies on polyphenol intake and longevity could provide valuable insights into optimal amounts and patterns of phytochemical consumption for supplement development. Until stronger evidence supports supplementation, consuming polyphenols through a healthy, balanced diet remains the safest and most effective approach.