Selenium (Se) is an essential trace element that plays a critical role in the biosynthesis of selenoproteins, which are involved in antioxidant defense, redox regulation, and thyroid hormone metabolism. While Se deficiency can be mitigated through diet or supplementation, excessive intake or uncontrolled self-supplementation may increase the risk of type 2 diabetes (T2D). Recent studies suggest a sex-specific relationship between Se status and T2D risk, with potentially increased risk in men and a protective effect in women, particularly for gestational diabetes mellitus (GDM). High Se status is associated with improved prognosis in T2D patients and reduced risk of macrovascular complications. However, the evidence is conflicting, with some studies indicating a potential risk of T2D from Se supplementation, while others show beneficial effects. The relationship between Se and T2D is complex, influenced by biological, hormonal, and environmental factors. Observational studies suggest that Se status is linked to T2D risk, with inverse associations in women and positive associations in men. Recent large-scale observational studies indicate that sufficient Se status is associated with improved survival and reduced mortality in T2D patients. However, data on microvascular complications remain limited. The review highlights the need for further research, particularly in understanding the molecular mechanisms underlying sex-specific effects and the role of Se in T2D prognosis and complications. The findings suggest that Se supplementation may be beneficial for women with Se deficiency but may increase T2D risk in men from Se-replete populations. The review emphasizes the importance of considering Se status, sex, and disease characteristics in the management of T2D.Selenium (Se) is an essential trace element that plays a critical role in the biosynthesis of selenoproteins, which are involved in antioxidant defense, redox regulation, and thyroid hormone metabolism. While Se deficiency can be mitigated through diet or supplementation, excessive intake or uncontrolled self-supplementation may increase the risk of type 2 diabetes (T2D). Recent studies suggest a sex-specific relationship between Se status and T2D risk, with potentially increased risk in men and a protective effect in women, particularly for gestational diabetes mellitus (GDM). High Se status is associated with improved prognosis in T2D patients and reduced risk of macrovascular complications. However, the evidence is conflicting, with some studies indicating a potential risk of T2D from Se supplementation, while others show beneficial effects. The relationship between Se and T2D is complex, influenced by biological, hormonal, and environmental factors. Observational studies suggest that Se status is linked to T2D risk, with inverse associations in women and positive associations in men. Recent large-scale observational studies indicate that sufficient Se status is associated with improved survival and reduced mortality in T2D patients. However, data on microvascular complications remain limited. The review highlights the need for further research, particularly in understanding the molecular mechanisms underlying sex-specific effects and the role of Se in T2D prognosis and complications. The findings suggest that Se supplementation may be beneficial for women with Se deficiency but may increase T2D risk in men from Se-replete populations. The review emphasizes the importance of considering Se status, sex, and disease characteristics in the management of T2D.