Diabetes mellitus (DM) is considered a global pandemic, and the incidence of DM continues to grow worldwide. Nutrients and dietary patterns are central issues in the prevention, development and treatment of this disease. The pathogenesis of DM is not completely understood, but nutrient-gene interactions at different levels, genetic predisposition and dietary factors appear to be involved. Nutritional genomics studies generally focus on dietary patterns according to genetic variations, the role of gene-nutrient interactions, gene-diet-phenotype interactions and epigenetic modifications caused by nutrients; these studies will facilitate an understanding of the early molecular events that occur in DM and will contribute to the identification of better biomarkers and diagnostics tools. In particular, this approach will help to develop tailored diets that maximize the use of nutrients and other functional ingredients present in food, which will aid in the prevention and delay of DM and its complications. This review discusses the current state of nutrigenetics, nutrigenomics and epigenomics research on DM. Here, we provide an overview of the role of gene variants and nutrient interactions, the importance of nutrients and dietary patterns on gene expression, how epigenetic changes and micro RNAs (miRNAs) can alter cellular signaling in response to nutrients and the dietary interventions that may help to prevent the onset of DM.