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 and excessive supplementation can have adverse health effects, the relationship between Se and type 2 diabetes (T2D) is complex and sex-specific. Recent evidence suggests that Se deficiency is associated with an increased risk of gestational diabetes mellitus (GDM), while higher Se status is linked to improved prognosis and reduced risk of macrovascular complications in T2D patients. However, a large randomized controlled trial (RCT) indicated that supplemental Se may increase T2D risk, raising concerns about its clinical application. Observational studies and experimental models have shown conflicting results, highlighting the need for further research. The relationship between Se and T2D appears to be influenced by various biological, hormonal, and environmental factors, with sex-specific effects observed. Men may be at higher risk of T2D with high Se intake, while women may benefit from Se supplementation, particularly in Se-deficient areas. The sex-specific association of Se with T2D risk and insulin resistance is an emerging area of research. Additionally, Se status is linked to improved outcomes in T2D patients, including lower all-cause and cardiovascular mortality, and reduced risk of macrovascular complications. However, the exact molecular mechanisms underlying these effects remain to be elucidated. Current evidence suggests that Se status is a significant modulator of T2D prognosis and complications, but the role of Se supplementation in clinical settings remains controversial. Large-scale observational studies have shown that higher Se status is associated with better outcomes in T2D patients, although data on microvascular complications are limited. The sex-specific effects of Se on T2D highlight the importance of considering individual variations in Se status and the need for further research to clarify the mechanisms and clinical implications of Se in T2D management. Future studies should focus on understanding the sex-specific effects of Se and its role in T2D prognosis and complications.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 and excessive supplementation can have adverse health effects, the relationship between Se and type 2 diabetes (T2D) is complex and sex-specific. Recent evidence suggests that Se deficiency is associated with an increased risk of gestational diabetes mellitus (GDM), while higher Se status is linked to improved prognosis and reduced risk of macrovascular complications in T2D patients. However, a large randomized controlled trial (RCT) indicated that supplemental Se may increase T2D risk, raising concerns about its clinical application. Observational studies and experimental models have shown conflicting results, highlighting the need for further research. The relationship between Se and T2D appears to be influenced by various biological, hormonal, and environmental factors, with sex-specific effects observed. Men may be at higher risk of T2D with high Se intake, while women may benefit from Se supplementation, particularly in Se-deficient areas. The sex-specific association of Se with T2D risk and insulin resistance is an emerging area of research. Additionally, Se status is linked to improved outcomes in T2D patients, including lower all-cause and cardiovascular mortality, and reduced risk of macrovascular complications. However, the exact molecular mechanisms underlying these effects remain to be elucidated. Current evidence suggests that Se status is a significant modulator of T2D prognosis and complications, but the role of Se supplementation in clinical settings remains controversial. Large-scale observational studies have shown that higher Se status is associated with better outcomes in T2D patients, although data on microvascular complications are limited. The sex-specific effects of Se on T2D highlight the importance of considering individual variations in Se status and the need for further research to clarify the mechanisms and clinical implications of Se in T2D management. Future studies should focus on understanding the sex-specific effects of Se and its role in T2D prognosis and complications.