Objectives: We aimed to evaluate the effects of acute and chronic aerobic exercise on cognitive function and depression levels in patients with Type 2 Diabetes Mellitus (T2DM) and the changes in related neurotrophic and metabotropic factors. Methods: Sixteen female patients (age=57.5 ± 7.3) diagnosedwith T2DMwere included. A and B sections of the Trail Making Test (TMT) and Beck Depression Inventory (BDI) were used to assess executive function and depression states. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), irisin, total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), fasting plasma glucose, hemoglobin A1c, and high-density lipoprotein (HDL) cholesterol were analyzed in blood. Aerobic exercise intensity was applied at 50–70% of the maximal heart rate for 40 min/day, three daysweekly on the treadmill. All evaluations were repeated after one exercise session, a 12-week exercise program, and after one year for follow-up. Results: TMT-A (p=0.001) and TMT-B (p=0.002) values were increased following both acute and chronic exercise. BDI scores were decreased after long-term exercise (p=0.031). Measurement of metabolic parameters revealed positive changes in HDL cholesterol (p=0.044), TAS (p=0.005), and OSI (p=0.009) values after chronic period exercise. No significant difference was found in BDNF (p=0.271), NGF (p=0.230), and irisin (p=0.101) values after acute or chronic exercise, on the other hand. Conclusions: Although aerobic exercise training had a positive effect on metabolic and cognitive outcomes, this effect was independent of neurotrophic and metabotropic factors. Regular and long-term aerobic exercise training has protective and regulatory functions in T2DM.