Background Magnesium, an essential dietary trace element, plays a crucial role in numerous physiological processes, and its deficiency has been associated with the development of hyperlipidemia. However, its potential to predict long-term outcomes and inform risk stratification in hyperlipidemic patients remains underexplored. Methods This retrospective cohort study introduces the magnesium depletion score (MgDS), a novel index for quantifying magnesium deficiency, and investigates its association with mortality outcomes in individuals with hyperlipidemia. Data from 12,592 participants in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 were analyzed. Advanced statistical methods, including weighted Cox proportional hazards models, restricted cubic spline (RCS) analysis, Kaplan–Meier survival curves, and receiver operating characteristic (ROC) analysis, were employed to assess the association between MgDS and mortality risks. Results The results indicate that higher MgDS is significantly associated with increased risks of both all-cause and cardiovascular mortality in individuals with hyperlipidemia, even after adjusting for confounders. Subgroup analyses identified prediabetes, smoking, and alcohol consumption as significant modifiers of this association. RCS analysis confirmed a linear relationship between MgDS and mortality, further supporting its value as a reliable predictor of long-term outcomes. ROC analysis demonstrated the potential of MgDS as an independent tool for predicting mortality at 1, 3, and 5 years. Notably, high MgDS levels in hyperlipidemic individuals with binge drinking habits were associated with significantly higher mortality risks. Conclusions These results establish MgDS as a promising biomarker for mortality risk stratification in patients with hyperlipidemia. This novel index offers important insights for clinical practice and could facilitate the development of tailored management strategies, particularly for high-risk hyperlipidemia populations, to mitigate long-term health risks. Graphical abstract