Results from a pilot project indicate that isoflavones and exercise could have an additive effect on body composition and clinical risk factors of CVD in postmenopausal women. The objective of the present study was to assess the combined effect of exercise and isoflavones in overweight-to-obese postmenopausal women. In this double-blind randomised controlled trial, 100 overweight-to-obese (BMI 29·9 (sd 3·2) kg/m2) postmenopausal women were assigned to four groups: (1) placebo (PLA); (2) isoflavones (ISO); (3) exercise and placebo (Ex+PLA); (4) exercise and isoflavones (Ex+ISO). The supplementation contained 70 mg/d of isoflavones. Exercise consisted of three weekly sessions of resistance training and aerobics. Outcome measures included fat mass (FM), lean body mass (LBM), bone mineral density, lipid profile, fasting glucose, fasting insulin and insulin resistance (homeostasis assessment model). The main effects of exercise were observed for total FM (P = 0·02), FM% (P < 0·01), trunk FM% (P = 0·05), arm FM% (P < 0·01), leg FM% (P = 0·02), arm LBM (P < 0·01), leg LBM (P = 0·02) and C-reactive protein (P < 0·01). A main effect was detected for isoflavones in improving leg FM% (P = 0·05). No interactions were observed between isoflavones and exercise. In conclusion, it was observed that 6 months of exercise brought favourable changes in total FM, FM% and LBM in overweight postmenopausal women. No synergistic effects were observed between exercise and isoflavones. However, isoflavones could have a beneficial effect on leg FM%.