Background: Beneficial effects of life style modification (exercise training and nutritional interventions) on improving the quality of life and health status, and preventing age-related pathologies is proven in epidemiologic studies. Objectives: The current randomized, double-blind, clinical trial aimed at evaluating the effects of a 12-week turmeric intake and Pilates training on serum level of SIRT 1, weight, and body fat percentage in postmenopausal females. Methods: The current clinical trial with a four-group design was conducted on 44 sedentary overweight females with the mean age of 50.3 ± 3.8 years randomly assigned to one of the groups receiving 1.5 mg/kg turmeric powder or placebo daily with or without Pilates training for 12 weeks. Serum SIRT1 level, body weight, and body fat percentage changes were analyzed before and 24 hours after the intervention. Pairwise t-test and one-way ANOVA were used for data analysis (P < 0.05). Results: According to the results, a 12-week Pilates and Pilates-turmeric intervention reduced weight and body fat percentage by~8% and 6% respectively, and increased serum SIRT1 content by~2.9 fold (P < 0.01) in the training groups compared with the control group. There were significant differences between the training groups in comparison with the control or turmeric groups in all dependent variables. There was no significant difference between the Pilates and Pilates-turmeric groups. Moreover, no significant difference was observed in dependent variables in the turmeric supplementation group compared with baseline measures or the control group (P ≥ 0.05). Conclusions: Three months of Pilates training with and without turmeric supplementation seemed effective in increasing SIRT1 and improving body composition in middle-aged females. However, the results did not support the hypothesis that turmeric intake alone has potential exercise like effects on healthy middle-aged females.