Background: Mediterranean diet has been demonstrated to exert beneficial effects toward various health outcomes. Among the compounds that may be responsible for such benefits, polyphenols have been proposed as potential candidates. The aim of this study was to evaluate whether dietary polyphenols were associated with adherence to the Mediterranean diet in a Sicilian cohort. Methods: A total of 1937 adults were recruited in the urban area of Catania, southern Italy. Background characteristics and dietary habits were collected through validated questionnaires. Adherence to the Mediterranean diet was evaluated through application of a validated score (MEDI-LITE score). Dietary intake of polyphenols was estimated through the Phenol-explorer database. Differences in mean intake between quartiles of the MEDI-LITE score and association between quartiles of polyphenol intake and high adherence to the Mediterranean diet (highest quartile of the score) were calculated though logistic regression analyses. Results: Mean intake of most polyphenols was significantly different between quartiles of the MEDI-LITE score, being generally higher in individuals more adherent to the Mediterranean diet. Only few compounds, such as lignans, anthocyanins, and flavanones, showed a linear positive association with high adherence to the Mediterranean diet, while other polyphenol classes were associated in a non-linear manner. Among individual polyphenols, apigenin, hesperetin, naringenin, lariciresinol, matairesinol, pinoresinol, secoisolariciresinol, and ferulic acid were associated with high adherence to Mediterranean diet in a linear manner, while all the others (except for myricetin) were associated in a non-linear way. Conclusions: Mean polyphenol intake was higher in individuals more adherent to the Mediterranean diet compared to less adherent. However, dietary sources of polyphenols not included in the traditional foods comprised in the Mediterranean diet may contribute to total and specific classes of polyphenols irrespectively of their inclusion within the context of the Mediterranean diet.