<p>Gestational diabetes mellitus (GDM) is a glucose metabolism disorder with an unclear etiology that occurs specifically during pregnancy. While elevated serum ferritin levels have been reported to increase the risk of GDM, these findings lack validation in large-scale studies and have yet to inform clinical practice effectively. This study enrolled 12,434 controls and 3599 GDM patients and employed binary multifactorial logistic regression, restricted cubic spline, propensity score matching, and a random forest algorithm to explore the relationship between serum ferritin and GDM, as well as the effect size of ferritin on GDM. The results indicated that GDM patients have higher serum ferritin levels compared to controls in the second and third trimesters. A weak correlation was found between serum ferritin levels and OGTT 1-hour and 2-hour blood glucose levels in the second trimester. Logistic regression (LR) and restricted cubic spline (RCS) analyses showed a significant positive correlation between serum ferritin levels and GDM in the second and third trimesters. Propensity score matching analysis indicated that the association between second-trimester serum ferritin levels and GDM remained nearly constant before and after matching. The random forest algorithm suggested that among all confounders, serum ferritin had a minimal effect on GDM risk. In conclusion, our study provides further compelling evidence for the association between serum ferritin levels and gestational diabetes mellitus. However, additional research is still needed to clarify the specific mechanisms underlying this association.</p>