Certain foods characterizing the alternate Mediterranean diet (aMED) are high in persistent organic pollutants (POPs), which are related to greater gestational diabetes mellitus (GDM) risk. We examined the associations of combined aMED and POP exposure with GDM. aMED score of 1,572 pregnant women was derived from food frequency questionnaires at early pregnancy within the U.S. Fetal Growth Study and plasma concentrations of 76 POPs, including organochlorine pesticides, polybrominated diphenyl ethers, polychlorinated biphenyls (PCBs), and per- and polyfluoroalkyl substances, were measured. Associations of combined aMED score and exposure to POPs with GDM risk were examined by multivariable logistic regression models. In 61 of 1,572 (3.88%) women with GDM, 25 of 53 included POPs had a detection rate >50%. Higher POP levels appeared to diminish potential beneficial associations of aMED score with GDM risk, with the lowest GDM risk observed among women with both high aMED score and low POP concentrations. Specifically, adjusted log-odds ratios of GDM risk comparing women with low PCB and high aMED score with those with low aMED score and high PCB concentrations was -0.74 (95% CI -1.41, -0.07). Inverse associations were also observed among women with low aMED score and high TransNo_chlor, PCB182_187, PCB196_203, PCB199, and PCB206. These associations were more pronounced among women with overweight or obesity. Pregnant women who consumed a healthy Mediterranean diet but had a low exposure to POP concentrations had the lowest GDM risk. Future endeavors to promote a healthy diet to prevent GDM may consider concurrent POP exposure.