Exposure to dichlorodiphenyldichloroethylene (DDE) is suspected to be associated with an increased risk of type 2 diabetes (T2D). Other studies suggested that the fat mass and obesity-associated gene (FTO) is associated with T2D risk, regardless of adiposity. Dichlorodiphenyltrichloroethane (DDT) was used in Brazil until the mid-2000s, but no previous studies investigated the association between diabetes and body concentrations of DDE in that country. We investigated that association in a population of Rio de Janeiro, as well as if the FTO-rs9939609 genotypes might affect it. In this cross-sectional study nested in the Pro-Saude cohort, participants were randomly selected according to age, sex, and educational level at the cohort’s baseline up to n = 511. Individuals who self-reported diabetes or presented glycated hemoglobin (HbA1c) ≥ 6.5% in the study’s phase 4 were considered diabetic. We used logistic regression to estimate the odds ratio of diabetes according to serum levels of DDE, adjusting for age, sex, and education. We stratified the adjusted odds ratio by FTO-rs9939609 variant genotypes. Serum levels of DDE were associated with a higher chance of having diabetes (OR: 1.44; 95%CI: 1.13–1.84). Across quartiles of DDE concentrations, the dose–response relationship was statistically significant (p-trend = 0.01). In addition, our results also suggest that the magnitude of this association is higher in individuals with the homozygous allele genotype for the rs9939609 variant of the FTO gene, which is highly associated with obesity and diabetes. Exposure to DDE may increase the risk of developing diabetes in the Brazilian population.