<p>Metallothioneins (MTs) are small cysteine-rich intracellular proteins. The best-known biological functions of MTs are sequestration of metal ions and maintenance of redox homeostasis. Despite these protective functions, it has been demonstrated that MTs are involved in tumorigenesis, cellular differentiation, drug resistance, and metabolic disorders such as diabetes and obesity, in which MTs expression is substantially deregulated in adipose tissue. In addition, many studies have experimentally evidenced a possible role of MTs in the development of diabetes. Given the rich biochemical properties of MTs, it can be concluded that they are involved in several aspects of development and progression of obesity and diabetes. Thus, evaluation of expression of MTs could serve as biomarker to personalize available therapeutic interventions and possibly to develop novel advanced therapeutic modalities. Overall, the purpose of this review is analyze and review the latest studies aimed on the multiple roles of MTs in metabolic disorders, possible use of MTs as obesity and diabetes biomarkers and the role of MTs in cardioprotection during diabetes progression.</p>