The redox reaction and energy metabolism status in mitochondria is involved in the pathogenesis of metabolic related disorder in kidney including diabetic kidney disease (DKD). Nicotinamide adenine dinucleotide (NAD⁺) is a cofactor for redox reactions and energy metabolism in mitochondria. NAD⁺ can be synthesized from four precursors through three pathways. The accumulation of NAD⁺ may ameliorate oxidative stress, inflammation and improve mitochondrial biosynthesis via supplementation of precursors and intermediates of NAD⁺ and activation of sirtuins activity. Conversely, the depletion of NAD⁺ via NAD⁺ consuming enzymes including Poly (ADP-ribose) polymerases (PARPs), cADPR synthases may contribute to oxidative stress, inflammation, impaired mitochondrial biosynthesis, which leads to the pathogenesis of DKD. Therefore, homeostasis of NAD⁺ may be a potential target for the prevention and treatment of kidney diseases including DKD. In this review, we focus on the regulation of the metabolic balance of NAD⁺ on the pathogenesis of kidney diseases, especially DKD, highlight benefits of the potential interventions targeting NAD⁺-boosting in the treatment of these diseases.