Context The association between magnesium status and metabolic syndrome (MetS) remains unclear.Objective This study aimed to examine the relationship between kidney reabsorption-related magnesium depletion score (MDS) and MetS among US adults.Methods We analyzed data from 15 565 adults participating in the National Health and Nutrition Examination Survey (NHANES) 2003 to 2018. MetS was defined according to the National Cholesterol Education Program's Adult Treatment Panel III report. The MDS is a scoring system developed to predict the status of magnesium deficiency that fully considers the pathophysiological factors influencing the kidneys' reabsorption capability. Weighted univariate and multivariable logistic regression were used to assess the association between MDS and MetS. Restricted cubic spline (RCS) analysis was conducted to characterize dose-response relationships. Stratified analyses by sociodemographic and lifestyle factors were also performed.Results In both univariate and multivariable analyses, higher MDS was significantly associated with increased odds of MetS. Each unit increase in MDS was associated with approximately a 30% higher risk for MetS, even after adjusting for confounding factors (odds ratio 1.31; 95% CI, 1.17-1.45). RCS graphs depicted a linear dose-response relationship across the MDS range. This positive correlation remained consistent across various population subgroups and exhibited no significant interaction by age, sex, race, adiposity, smoking status, or alcohol consumption.Conclusion Higher urinary magnesium loss as quantified by MDS may be an independent linear risk factor for MetS in US adults, irrespective of sociodemographic and behavioral factors. Optimizing magnesium nutritional status could potentially confer benefits to patients with MetS.