There is evidence that a change in lifestyle, especially physical activity and diet, can reduce the risk of developing type-2 diabetes mellitus (T2DM). However, the response to dietary changes varies among individuals due to differences in metabolic characteristics. Therefore, we investigated the association between dietary patterns and T2DM while taking into account these differences. For 1287 participants of the population-based KORA FF4 study (Cooperative Health Research in the Region of Augsburg), we identified three metabolically-homogenous subgroups (metabotypes) using 16 clinical markers. Based on usual dietary intake data, two diet quality scores, the Mediterranean Diet Score (MDS) and the Alternate Healthy Eating Index (AHEI), were calculated. We explored the associations between T2DM and diet quality scores. Multi-variable adjusted models, including metabotype subgroup, were fitted. In addition, analyses stratified by metabotype were carried out. We found significant interaction effects between metabotype and both diet quality scores (p< 0.05). In the analysis stratified by metabotype, significant negative associations between T2DM and both diet quality scores were detected only in the metabolically-unfavorable homogenous subgroup (Odds Ratio (OR) = 0.62, 95% confidence interval (CI) = 0.39-0.90 for AHEI and OR = 0.60, 95% CI = 0.40-0.96 for MDS). Prospective studies taking metabotype into account are needed to confirm our results, which allow for the tailoring of dietary recommendations in the prevention of T2DM.