Background <p>Diabetes and metabolic syndrome are major public health challenges closely linked to oxidative stress, inflammation, and impaired insulin signaling. Selenium, an essential trace element with antioxidant and immunomodulatory roles, has been proposed as an adjunctive strategy for metabolic regulation; however, evidence from randomized trials remains inconsistent. We evaluated the effects of selenium supplementation on glycemic indices, oxidative-stress-related biomarkers, lipid metabolism, and related metabolic indicators in adults, and explored potential effect modifiers.</p> Methods <p>We searched PubMed, Embase, Cochrane CENTRAL, Web of Science, CINAHL, CNKI, WanFang, VIP, and SinoMed through 12 August 2025 for randomized controlled trials of oral selenium supplementation in adults, including pregnant women with gestational diabetes mellitus (GDM). Outcomes included fasting plasma glucose, glycated hemoglobin, fasting insulin, indices of insulin resistance and β-cell function, oxidative-stress-related and inflammatory biomarkers, lipid parameters, and anthropometric and hemodynamic indicators. Random-effects meta-analyses estimated weighted mean differences with 95% confidence intervals. Subgroup, dose-response, and sensitivity analyses were performed, and certainty of evidence was assessed using GRADE.</p> Results <p>Fifty-two treatment arms involving 10,916 participants were included. Selenium supplementation reduced fasting insulin, HOMA-IR, and HOMA-β values and increased QUICKI, but showed no clear overall effect on fasting plasma glucose or glycated hemoglobin. Favorable changes were observed in selected antioxidant and inflammatory biomarkers, including increases in glutathione, total antioxidant capacity, superoxide dismutase, glutathione peroxidase, and serum selenium, and reductions in malondialdehyde and high-sensitivity C-reactive protein, with no clear effect on nitric oxide. Modest changes in lipid parameters were also observed, including higher high-density lipoprotein cholesterol and lower low-density lipoprotein cholesterol, triglycerides, and total cholesterol. Among anthropometric and hemodynamic outcomes, only diastolic blood pressure was reduced. Effects varied by dose, duration, participant characteristics, and geographical selenium exposure context.</p> Conclusions <p>Selenium supplementation was associated with modest improvements in insulin-sensitivity markers, selected antioxidantand inflammatory biomarkers, and lipid parameters, while showing no clear overall effect on fasting plasma glucose or glycated hemoglobin. These findings may be most applicable to populations with marginal or low baseline selenium status and should be extrapolated cautiously to selenium-replete settings. Long-term, high-quality RCTs are needed to clarify baseline-status-specific effects, safe dose ranges, and long-term safety.</p> Trial registration <p>PROSPERO CRD420251124852.</p>