Type 2 diabetes (T2D) is a rapidly growing epidemic, which leads to increased mortality rates and health care costs. Nutrients (namely, carbohydrates, fat, protein, mineral substances, and vitamin), sensing, and management are central to metabolic homeostasis, therefore presenting a leading factor contributing to T2D. Understanding the comprehensive effects and the underlying mechanisms of nutrition in regulating glucose metabolism and the interactions of diet with genetics, epigenetics, and gut microbiota is helpful for developing new strategies to prevent and treat T2D. In this review, we discuss different mechanistic pathways contributing to T2D and then summarize the current researches concerning associations between different nutrients intake and glucose homeostasis. We also explore the possible relationship between nutrients and genetic background, epigenetics, and metagenomics in terms of the susceptibility and treatment of T2D. For the specificity of individual, precision nutrition depends on the person’s genotype, and microbiota is vital to the prevention and intervention of T2D.