Growing evidence shows that a dietary pattern inspired by Mediterranean diet principles is associated with numerous health benefits. A Mediterranean-type diet has been demonstrated to exert a preventive effect toward cardiovascular diseases, in both Mediterranean and non-Mediterranean populations. Part of these properties may depend on a positive action toward healthier metabolism, decreasing the risk of diabetes and metabolic-syndrome-related conditions. Some studies also suggested a potential role in preventing certain cancers. Finally, newer research has showed that a higher adherence to the Mediterranean diet is associated with a lower risk of cognitive decline, depression, and other mental disorders. Overall, a better understanding of the key elements of this dietary pattern, the underlying mechanisms, and targets, are needed to corroborate current evidence and provide insights on new and potential outcomes.This Special Issue welcomes original research and reviews of literature concerning the Mediterranean diet and various health outcomes: Observational studies on established nutritional cohorts (preferred), case-control studies, or population sample on the association with non-communicable diseases;Level of evidence on the association with human health, including systematic reviews and metaanalyses; Evaluation of application of Mediterranean diet principles in non- Mediterranean countries;Description of mechanisms of action, pathways, and targets at the molecular level, including interaction with gut microbiota.