IntroductionWomen’s mental health has a significant impact on the health of society. Due to the prevalence of mental health problems in women with PCOS, this study aimed to determine the effect of cognitive behavioral therapy on depression and anxiety (primary outcomes) and quality of life (secondary outcomes) in women with polycystic ovary syndrome.MethodsThis randomized controlled trial was performed on 84 patients with PCOS referred to Al-Zahra Hospital in Tabriz-Iran, 2021. Participants were randomly assigned to intervention (n = 42) and control (n = 42) groups. Counseling with cognitive behavioral therapy was provided in 8 sessions of 60–90 min weekly in groups with 5 to 7 people in each group for the intervention group. Spielberger State-Trait Anxiety, Beck Depression, and Quality of Life Questionnaire for women with polycystic ovary syndrome (PCOSQ) were used to collect data. Independent t-test and ANCOVA were used to compare the outcomes between the two groups.ResultsAfter the intervention, based on ANCOVA test with adjusting the baseline values, mean scores of depression (mean difference (MD): -18.6; 95% confidence interval (95% CI): -19.4 to -17.8: P < 0.001), trait anxiety (MD: -15.0; 95% CI: -16.0 to -13.9; P < 0.001), and state anxiety (MD: -15.3; 95% CI: -16.2 to -14.3; P < 0.001), were significantly lower in the intervention group compared to the control group. The mean score of quality of life (MD: 19.25; 95% CI: 17.66 to 20.84; P < 0.001) was significantly higher in the intervention group compared to the control group.ConclusionThis study showed that CBT was effective in reducing depression and anxiety and improving the quality of life. Therefore it is recommended that health care providers use this approach to improve the mental health and quality of life of women with PCOS.Trial registrationIranian Registry of Clinical Trials (IRCT): IRCT20110826007418N7. Date of registration: 25/10/2021. URL:https://en.irct.ir/trial/57348; Date of first registration: 25/10/2021.