BACKGROUND/OBJECTIVES: With the increasing life expectancy and, as a result, the aging of the global population, there has been a rise in the prevalence of chronic conditions, which can significantly impact individuals' health-related quality of life, a multidimensional concept that comprises an individual's physical, mental, and social wellbeing. While a balanced, nutrient-dense diet, such as Mediterranean diet, is widely recognized for its role in chronic disease prevention, particularly in reducing the risk of cardiovascular diseases and certain cancers, its potential benefits extend beyond these well-known effects, showing promise in improving physical and mental wellbeing, and promoting health-related quality of life. METHODS: A systematic search of the scientific literature in electronic databases (Pubmed/Medline) was performed to identify potentially eligible studies reporting on the relation between adherence to the Mediterranean diet and health-related quality of life, published up to December 2024. RESULTS: A total of 28 studies were included in this systematic review, comprising 13 studies conducted among the general population and 15 studies involving various types of patients. Overall, most studies showed a significant association between adherence to the Mediterranean diet and HRQoL, with the most significant results retrieved for physical domains of quality of life, suggesting that diet seems to play a relevant role in both the general population and people affected by chronic conditions with an inflammatory basis. CONCLUSIONS: Adherence to the Mediterranean diet provides significant benefits in preventing and managing various chronic diseases commonly associated with aging populations. Furthermore, it enhances the overall health and quality of life of aging individuals, ultimately supporting more effective and less invasive treatment approaches for chronic diseases.