We investigated the effect of an antenatal lifestyle intervention of a low-glycaemic index (GI) diet and physical activity on energy-adjusted dietary inflammatory index (E-DIITM) and explored its relationship with maternal and child health in women with overweight and obesity. This was a secondary analysis of 434 mother−child pairs from the Pregnancy Exercise and Nutrition Study (PEARS) trial in Dublin, Ireland. E-DIITM scores were calculated for early (10–16 weeks) and late (28 weeks) pregnancy. Outcomes included lipids, inflammation markers, insulin resistance, mode of delivery, infant size, pre-eclampsia, and gestational diabetes. T-tests were used to assess changes in E-DIITM. Chi-square, correlations, and multiple regression were employed to investigate relationships with outcomes. The mean (SD) age of participants was 32.45 (4.29) years with median (IQR) BMI 28.25 (26.70, 31.34) kg/m2. There was no change in E-DIITM in the controls (−0.14 (1.19) vs. −0.07 (1.09), p = 0.465) but E-DIITM reduced by 10% after the intervention (0.01 (1.07) vs −0.75 (1.05), p < 0.001). No associations were found between early pregnancy E-DIITM and maternal and child outcomes, except for increased odds of adverse cardiometabolic phenotype in women who delivered male (OR = 2.29, p = 0.010) but not female infants (OR = 0.99, p = 0.960). A low-GI antenatal intervention can reduce the inflammatory potential of diets. Sex differences should be explored further in future research.