Mediterranean Diet, Polyphenols, and Neuroprotection: Mechanistic Insights into Resveratrol and Oleuropein

Background: Neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease, are among the leading causes of disability and mortality worldwide. Dietary patterns have emerged as modifiable risk factors that may influence disease onset and progression. The Mediterranean diet (MedDiet), rich in fruits, vegetables, whole grains, legumes, fish, and extra virgin olive oil, has been consistently associated with better cognitive outcomes and reduced risk of neurodegeneration. Aim: This narrative review summarizes current evidence on the role of the MedDiet in slowing the progression of neurodegenerative diseases, with a particular focus on polyphenols such as resveratrol and oleuropein as key bioactive mediators. Methods: We synthesized findings from epidemiological studies, clinical trials, and mechanistic research to provide an integrated overview of how adherence to the MedDiet and its polyphenol components affects neurodegenerative disease trajectories. Results: Epidemiological studies suggest that higher MedDiet adherence is associated with slower cognitive decline, reduced conversion from mild cognitive impairment to Alzheimer’s disease, and better motor and non-motor outcomes in Parkinson’s disease. Mechanistically, the MedDiet modulates oxidative stress, neuroinflammation, mitochondrial function, vascular health, and the gut–brain axis. Polyphenols such as resveratrol and oleuropein exert neuroprotective effects through antioxidant activity, modulation of amyloid aggregation, mitochondrial biogenesis, and activation of signaling pathways (e.g., SIRT1). Clinical studies, although limited, indicate beneficial effects of polyphenol-rich interventions on cognitive and metabolic biomarkers. Conclusions: Current evidence supports the Mediterranean diet as a promising dietary strategy to slow the progression of neurodegenerative diseases. Polyphenols, including resveratrol and oleuropein, may play a role in mediating these effects. Further well-designed, long-term clinical trials are needed to establish causal relationships, optimize dosage, and explore biomarker-driven personalized nutrition approaches.