<p>This study aimed to evaluate the effects of FTO (rs9939609) and ADRB3 (rs4994) gene variants, dietary intervention, and physical activity on gestational weight gain and perinatal outcomes in women with obesity and early gestational diabetes (GDM). In this prospective study, 115 pregnant women with obesity and early GDM were enrolled. All participants received standardised dietary counselling and recommendations regarding physical activity. Gestational weight gain, biochemical parameters, physical activity levels, genetic variants, and maternal and neonatal outcomes were assessed throughout pregnancy. Appropriate gestational weight gain was achieved by 73% of participants. Both earlier diagnosis of GDM (11 vs 14&#xa0;weeks, p = 0.04) and initiation of dietary intervention (12 vs 15&#xa0;weeks, p = 0.01) were observed in the group with recommended gestational weight gain. Women with EGWG had significantly higher glycated haemoglobin (HbA1c) levels in the second (5.03% vs 5.22%, p = 0.02) and third (5.33% vs 5.55%, p = 0.02) trimesters. Unfavourable FTO genotypes were associated with higher first-trimester HbA1c concentrations (p = 0.04) and elevated triglyceride levels throughout pregnancy (p &lt; 0.05) but were not independently associated with gestational weight gain. Higher physical activity in each trimester, was significantly associated with appropriate gestational weight gain regardless of genetic predisposition (p &lt; 0.001). Appropriate gestational weight gain was associated with a lower risk of neonatal macrosomia (2% vs 4%, p = 0.04). Among women with obesity and early GDM early dietary intervention and sustained physical activity were more strongly associated with appropriate gestational weight gain than the studied genetic variants. Appropriate gestational weight gain was associated with a lower risk of neonatal macrosomia.</p><p>Trial registration number and date of registration: NCT04924738, 14/06/2021</p>