Introduction: Uterine leiomyoma (uterine fibroids, UF) are benign myometrial tumors affecting up to 70% of women and may cause significant symptoms. Their pathogenesis involves cytokines, steroid hormones, growth factors, and increased extracellular matrix deposition and remodeling, though it is not fully understood. Recent evidence associates low vitamin D levels with higher prevalence and severity of myomas. This clinical trial evaluates the effect of nutritional supplement on UF. Material and Patients: Sixty (60) patients with uterine myoma received in a double-blind clinical trial for 16 weeks a nutritional formulation containing the omega 3 fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) 150 and 240 mg respectively, the selective pro resolving mediators (SPMs) 17-HDHA 180 µg, 18-HEPE 168 µg, 14-HDHA 90 µg, and vitamin D3 50 µg and vitamin B6 10 mg compared to placebo. The main outcomes were the development of bleeding, dysmenorrhea, volume reduction and quality of life assessment including female sexual desire. Results: The group receiving the nutritional showed a significant improvement in the parameters bleeding reduction, dysmenorrhea’s and female sexual function compared to placebo. No changes could be observed regarding the volume reduction and estradiol values between the groups. Conclusions: The nutritional containing Omega 3 fatty acid, SPMs, vitamin D and B6 represent a valid option for the symptomatic management of patients with uterine fibroids without comprising the hypothalamic pituitary axis of the women. Further research in grater groups of patients is needed to validate these first results.