Obesity, defined by BMI, is an escalating health concern. Selenium is an essential trace mineral involved in many metabolic activities, including the production of antioxidant enzymes, fat accumulation, and the conversion of inactive thyroid- T4 to the active form- T3, all of which impact BMI. However, little is known about the relationship between selenium and BMI. Furthermore, the impact of menopause, T3, and physical activity on this relationship has not been evaluated. This study aimed to 1) map the currently available evidence on the selenium level and BMI using Arksey and O’Malley’s scoping review framework, 2) investigate the relationship between serum selenium, BMI, and the menopausal status in 2,130 women who participated in the National Health and Nutrition Examination Survey (NHANES 2011-2012), and 3) analyze mediating effects of T3 and physical activity in the selenium and BMI relationship in 1,341 NHANES (2011-2012) adult participants. This cross-sectional study applied descriptive statistics, t-test, multiple linear regression models, and multilevel structural equation modeling for analysis. The scoping review identified conflicting findings, ranging from an inverse association between selenium to BMI to the positive association of low selenium with overweight and obesity. Adjusted for demographic factors, no statistically significant relationship between selenium and BMI, menopause, T3, or physical activity was found in our analysis. Postmenopausal women in our study had a significantly higher prevalence of obesity than premenopausal women while consuming significantly fewer calories per day. Men in our study had lower BMI, higher selenium and T3 levels, higheriv daily caloric intake, and lower activity levels than women participants. Future studies need to 1) identify and evaluate other metabolically important factors as potential mediating variables, 2) employ a longitudinal study design to capture changes in selenium, T3, and PA over time, and 3) include populations with selenium deficiency and selenium-replete participants to capture a broader range of serum levels and their effects on BMI values.