Endocrine disrupting chemicals (EDCs) have widespread environmental distribution originated from both natural and anthropogenic sources. From the last few decades, their contamination has been raised dramatically owing to continuous discharge in sewage and untreated industrial effluents. They have rapidly gained a considerable attention due to their critical role in the development of multiple endocrine-related disorders notably diabetes mellitus (DM). Cadmium and arsenic, among the most hazardous EDCs, are not only widely spread in our environment, but they are also found to be associated with wide range of health hazards. After entering into the human body, they are preferably accumulated in the liver, kidney and pancreas where they exhibit deleterious effects on carbohydrate metabolism pathways notably glycolysis, glucogenesis and gluconeogenesis through the modification and impairment of relevant key enzymes activity. Impairment of hepatic glucose homeostasis plays a crucial role in the pathogenesis of DM. Along with compromised function of pancreas and muscles, diminished liver and kidney functions also contribute considerably to increase the blood glucose level. These metals have potential to bring conformational changes in these enzymes and make them inactive. Additionally, these metals also disturb the hormonal balance, such as insulin, glucocorticoids and catecholamines; by damaging pancreas and adrenal gland, respectively. Moreover, these metals also enhance the production of reactive oxygen species and depress the anti-oxidative defense mechanism with subsequent disruption of multiple organs. In this article, we have briefly highlighted the impact of arsenic and cadmium on the metabolism of carbohydrates and the enzymes that are involved in carbohydrate metabolism and glucose homeostasis.