Objective: The study aimed to analyze the influence of physical activity levels and the rs9939609 polymorphism (FTO gene) on anthropometric, hemodynamic, and cardiac autonomic variables in public school students. Methods: A total of 288 students (aged 11 to 18, both sexes) from public schools in São Luís, Maranhão, were divided into four groups: sedentary AA+AT (AA+AT sed), active AA+AT (AA+AT activ), sedentary TT (TT sed), and active TT (TT activ). Evaluations included the International Physical Activity Questionnaire, weight, height, body mass index (BMI), buccal cells collection for DNA extraction, systolic (SBP) and diastolic (DBP) blood pressure measurements, and heart rate variability (HRV) analysis. A chi-square test for allelic associations was applied a 5% significance level. Results: No significant differences were observed in DBP or heart rate (HR). The active groups (AA+AT activ and TT activ) exhibited reductions in weight and METs/min/week compared to their respective sedentary groups (P<0.05). The TT activ group also demonstrated reductions in SBP and BMI compared to the TT sed group (P<0.05). The TT activ group had higher HRV in the RR time domain (ms) compared to the TT sed group (P<0.05), though no significant differences were found in other HRV variables. Conclusions: The FTO gene polymorphism influences cardiac autonomic modulation, while physical activity levels affect anthropometric variables.