Study question Does combinations therapy of insulin sensitizing agents, antioxidants and vitamins are safe and efficacious in PCOS patients. Summary answer Combination therapy of inositols, antioxidants and vitamins is safe and effective non-hormonal treatment option to manage PCOS. What is known already Monotherapy of insulin sensitising agents, antioxidants and vitamins is beneficial in the treatment of PCOS. Nutritional supplement containing inositols, N-acetylcysteine (NAC), lycopene, chromium picolinate, vitamin D3, biotin and folic acid treatment resulted in a significant improvement in menstrual cyclicity, acne and hirsutism. But there is no evidence pertaining to the hormonal parameters and ovarian morphology. Therefore, the present investigation was planned to evaluate the effects of combination therapy of inositols, antioxidants and vitamins on sign and symptoms, metabolic and hormonal parameters in women with PCOS. Study design, size, duration Multicentric, retrospective, observational cohort study was planned for the first time at thirty-six fertility clinics in different states of India from April 2019 to November 2020. Both lean and obese patients (16–39 years; n = 180) with confirmed diagnosis of PCOS as per the Rotterdam/ESHRE criteria were included in study. Participants/materials, setting, methods Patients were received a combination therapy of insulin sensitizers, antioxidants and vitamins in a marketed formulation (Trazer F ForteTM) twice daily as a tablet for 3 months and thereafter ovulation induction was done using letrozole (2.5–5 mg). Primary outcomes were improvements in signs of PCOS (menstrual cyclicity or ovulation restoration, acne and hirsutism), body weight, body mass index, waist circumference, ovarian cysts, pregnancy rate and hormonal balance. Secondary outcome was the evaluation of side effects. Main results and the role of chance Combination therapy of Trazer F ForteTM containing insulin sensitising agents (inositols, NAC and chromium), antioxidants (NAC and lycopene), and vitamins (vitamin D, biotin and folic acid) showed significant improvement in menstrual cyclicity by 54.3% and 88.2% in obese PCOS cases, and 48.7% and 79.5% in lean PCOS cases after 3- and 6-month of intervention respectively. Significant improvement was observed in acne, hirsutism and ovarian cysts post-intervention in both obese and lean PCOS women. After successful completion of the treatment, significant corrections were observed in metabolic (fasting glucose, fasting insulin and HOMA-IR) and hormonal profile (free testosterone, LH:FSH ratio, AMH and progesterone) in obese as well as lean PCOS cases. The clinical pregnancy rate was 16.2% and 34.1% in obese women, and 9.9% and 22.1% in lean cases after 3- and 6-month of intervention respectively. Limitations, reasons for caution Prevalent of PCOS is different in different population in India with diverse ethnic background. Hence, community-based intervention studies on larger population are needed to assess the efficacy and safety of such combinations amongst different age groups of women with PCOS. Wider implications of the findings: Since, PCOS is a multifactorial disorder, combined use of inositols, antioxidants and vitamins can be used as a promising and clinically relevant non-hormonal treatment option for the management of PCOS. Trial registration number NA