Toxic metals affecting metabolic pathways have a broad range in the ecosystem from both natural and anthropogenic sources. Because of constant contamination from waste and untreated chemical effluents, their emissions have risen significantly over the last few decades, quickly gaining attention due to their crucial role in the development of several metabolic disorders, notably diabetes mellitus. Cadmium and arsenic not only spread widely in our atmosphere but are also linked to a wide range of health hazards. These are primarily accumulated in the liver, kidney, and pancreas once they reach the human body, where they have deleterious effects on the metabolism of glucose and its association with other metabolic pathways, particularly glycolysis, glycogenesis, and gluconeogenesis, by altering and impairing the specific activity of major enzymes. Impairment of hepatic glucose homeostasis plays a crucial role in diabetes mellitus pathogenesis. Impaired liver and kidney functions, as well as decreased pancreatic and muscle function, also contribute significantly to elevated levels of blood glucose. Heavy metals have the potential to cause changes in the conformation in these enzymes. They also impair hormonal balance by destroying the pancreas and adrenal glands. Such metals often facilitate the development of reactive oxygen species and inhibit antioxidant defense mechanisms, with multiple organs subsequently damaged. This review briefly discusses the involvement of heavy metals in metabolic disorders such as diabetes mellitus, the enzymes involved in this pathway, and glucose homeostasis.