Nutrigenomic approaches based on ethnopharmacology and phytotherapy concepts have revealed that type 2 diabetes mellitus (T2DM) may be susceptible to dietary intervention. Interaction between bioactive food components and the genome may influence cell processes and modulate the onset and progression of the disease. T2DM, characterized by insulin resistance and beta cell dysfunction, is one of the leading causes of death and disability. Despite the great advances that have been made in the understanding and management of this complex, multifactorial disease, T2DM has become a worldwide epidemic in the 21st century. Population and family studies have revealed a strong genetic component of T2DM, and a number of candidate genes have been identified in humans. Variations in the gene sequences such as single nucleotide polymorphisms, explain the individual differences in traits like disease susceptibility and response to treatment. A clear understanding of how nutrients affect the expression of genes should facilitate the development of individualized intervention and, eventually, treatment strategies for T2DM. Review of the literature identified many phytochemicals/extracts from traditional medicinal plants that can target diabetogenic genes. This review focuses on the genetic aspects of T2DM, nutrient modification of genes relevant for diabetes, and future prospects of nutritional therapy of T2DM.