Introduction: Aging and obesity have common symptoms, including glucose and lipid metabolism changes. Activation of sirtuin 1 and FOXO1 (Forkhead Box Protein O1) can positively affect metabolic disorders associated with aging and obesity. This research aimed to investigate 16 weeks of combined exercise on the plasma levels of sirtuin 1, FOXO1, and glucose homeostasis in obese elderly. Methods: 40 obese elderly men with an average age of 61.90 ± 2.84 were selected and randomly divided into two experimental and control groups. The participants trained three days a week (each session 90 minutes) for 16 weeks. 48 hours before and after exercise, anthropometric characteristics and plasma values of sirtuin 1, FOXO1, fasting blood sugar, insulin, HOMA-IR (Homeostatic Model Assessment for Insulin Resistance), and HOMA-B (Homeostasis Model Assessment of β-Cell) were taken from the samples and measured by ELISA method. Data analysis was done using SPSS 16 software, independent and dependent t-tests at a significance level of P˂ 0.05. Results: Levels of fasting blood sugar (P=0.04), and insulin (P=0.008) in the experimental group decreased significantly compared to the control group, while the serum levels of sirtuin1 (P=0.0001) and FOXO1 (P=0.0001) had a significant increase. Correlated t results in the experimental group showed a significant decrease in insulin, HOMA-IR, and HOMA-B (P = 0.001) and a significant increase in the serum levels of sirtuin1 (P = 0.0001) and FOXO1 (P = 0.0001) (P ˂ 0.05). Conclusion: Based on the results of this study, it seems that 16 weeks of combined training has a favorable effect on improving glucose homeostasis, increasing sirtuin 1 and FOXO1 levels in elderly obese men.