Aim In postmenopause, ovarian decline along with sedentary lifestyle could contribute to the loss of lean body mass (LBM) and muscle strength. This study aimed to verify whether exercise and isoflavones could have additive effects on muscle quality, muscle mass index, relative strength and physical capacity in overweight sedentary postmenopausal women. Method We recruited 70 overweight-to-obese (body mass index 32.2 +/- 4.8 kg/m(2)) postmenopausal women (59 +/- 5 years old) to participate in a 6-month clinical study combining isoflavones (70 mg/day) and exercise (resistance and aerobic training) treatments. Subjects were divided into four groups: (1) placebo (n = 15), (2) isoflavones (n = 15), (3) exercise and placebo (n = 20), and (4) exercise and isoflavone (n = 20). Principal outcome variables included maximal muscle strength (1RM) at the leg press and the bench press, muscle mass index, muscle quality in the legs and relative strength. Results After 6 months of training, exercise produced 49% and 23% increases, respectively, in leg press and bench press 1RM (p <= 0.01). Leg relative strength and muscle quality increased by more than 50% (both p < 0.01), while muscle mass index increased by 7% (p < 0.05) in both exercise groups only. Conclusion Exercise training can improve muscle tissue strength, function and quality in sedentary postmenopausal women. Isoflavones, irrespective of exercise, did not produce changes in these variables. From a clinical perspective, these results suggest that overweight women could reduce the risks of mobility impairments, even in the absence of weight loss, by following a sound exercise intervention that includes both resistance and aerobic training at a high intensity.