Diabetes Mellitus, regarded as a silent killer, has been demonstrated to be a prime global health concern with a projected rise in prevalence from 171 million in 2010 to 366 million in 2030. Correspondingly, dietary management has shown to be a cornerstone modality in the attainment of good glycemic control in diabetes, and Nutrition/Diet remains a key player in diabetes prevention and management. In this light, of course, evidences from prospective observational studies, clinical trials and experimental findings have reported ameliorating ability of a number foods and nutrient on diabetes. However, a major concern is the genetic variability of individuals and their responses to these functional foods. Therefore, it has become necessary to understand how nutrients act at the molecular level which in turn involves a cascade of nutrient-related interactions at the gene, protein and metabolic levels. Overall, a Nutrigenomic approach provides; a snapshot showing genes that are switched on/off (the genetic potential) at any given moment, and the method to determine the influence of nutrients on gene/protein expression. Nutrigenomic has opened a new future to screen the genetic background, to monitor the transcriptome, proteome and metabolome and to ultimately develop dietary strategies which are targeted to supply the optimum nutrition and therapeutics for single individuals. Therefore, it is vital to support researches in the field of nutrigenomics in response to the prevalence of diabetes mellitus. Hence, the present review provides an understandings vis-à-vis the role of nutrient-gene interactions in diabetes, treatment, prevention and pathogenesis.