Objective: This study was designed to evaluate the effects of equol and resveratrol supplementation on health-related quality of life (HRQoL) in otherwise healthy menopausal women with hot flashes, anxiety and depressive symptoms. Methods: Sixty recently menopausal women aged 50-55 years were randomized in a 12-week, placebo controlled trial to receive 200 mg of fermented soy containing 10 mg of equol and 25 mg of resveratrol (1 tablet/day). The primary outcome was the change in score on the Menopause Rating Scale (MRS), used to evaluate the severity of age-/menopause-related complaints. Additional outcome measures included the subject-reported score on the Hamilton Rating Scale for Depression (HAM-D) and Nottingham Health Profile (NHP), which was used specifically to assess sleep quality. Results: The symptoms assessed by the MRS improved during treatment in the active group. Comparison between placebo and treatment groups revealed statistically significant improvement in particular for dryness of vagina (-85.7%) (p < 0.001), heart discomfort (-78.8%; p < 0.001) and sexual problems (-73.3%; p < 0.001). On the HAM-D significant improvements at week 12 were seen in work and activities (-94.1%) (p < 0.001). Subjects treated with equol and resveratrol also had significant differences in the sleep domain of the NHP (p < 0.001). Conclusion: These findings provide evidence that 12 weeks of dietary supplementation with equol and resveratrol may improve menopause-related quality of life in healthy women. (C) 2016 Elsevier Ireland Ltd. All rights reserved.