Platelet-activating factor (PAF) is a glycerylether lipid and one of the most potent endogenous mediators of inflammation. Through its binding to a well-characterized receptor it initiates a plethora of cellular pro-inflammatory actions participating by this way to the pathology of most chronic diseases, including cardiovascular and renal diseases, CNS decline and cancer. Among the variety of prudent dietary patterns, Mediterranean Diet (MD) is the dietary pattern with the strongest evidence for its ability to prevent the same chronic diseases. In addition, micronutrients and extracts from several components and characteristic food of the MD can favorably modulate PAF's actions and metabolism either directly or indirectly. However, the role of this traditional diet on PAF metabolism and actions has rarely been studied before. This systematic review summarizes, presents and discusses the outcomes of epidemiologic and intervention studies in humans, investigating the relationships between PAF status and MD. Seventeen full-text articles trying to interlink the components of MD and PAF are found and presented. The results are inconsistent due to the variability of the measured indices and methodology followed. However, preliminary results indicate that the characteristic "healthy" components of the MD, especially, cereals, legumes, vegetables, fish and wine can favorably modulate the pro-inflammatory actions of PAF and regulate its metabolism. Larger, well-controlled studies are necessary to elucidate whether the attenuation of PAF actions can mediate the preventive properties of MD against chronic diseases.