ScopeEvidence on the Mediterranean diet (MD) and age‐related cognitive decline (CD) is still inconclusive partly due to self‐reported dietary assessment. The aim of the current study is to develop an MD‐ metabolomic score (MDMS) and investigate its association with CD in community‐dwelling older adults.Methods and resultsThis study includes participants from the Three‐City Study from the Bordeaux (n = 418) and Dijon (n = 422) cohorts who are free of dementia at baseline. Repeated measures of cognition over 12 years are collected. An MDMS is designed based on serum biomarkers related to MD key food groups and using a targeted metabolomics platform. Associations with CD are investigated through conditional logistic regression (matched on age, sex, and education level) in both sample sets. The MDMS is found to be inversely associated with CD (odds ratio [OR] [95% confidence interval (CI)] = 0.90 [0.80–1.00]; p = 0.048) in the Bordeaux (discovery) cohort. Results are comparable in the Dijon (validation) cohort, with a trend toward significance (OR [95% CI] = 0.91 [0.83–1.01]; p = 0.084).ConclusionsA greater adherence to the MD, here assessed by a serum MDMS, is associated with lower odds of CD in older adults.