Fibromyalgia (FM) is a chronic disorder characterized by widespread musculoskeletal pain, fatigue, and cognitive impairment. Despite the availability of various treatment options, FM remains a challenging condition to manage. In the present study, we investigated the efficacy of formulated nanodispersions of lutein and beta-carotene in treating FM-related symptoms induced by reserpine in female Wistar rats. Several techniques have been implemented to assess this efficacy at various levels, including biochemical, bioelectrical, and behavioral. Namely, oxidative stress markers, monoamine levels, electrocorticography, pain threshold test, and open field test were conducted on control, FM-induced, and FM-treated groups of animals. Our results provided compelling evidence for the efficacy of carotenoid nanodispersions in treating FM-related symptoms. Specifically, we found that the dual action of the nanodispersion, as both antioxidant and antidepressant, accounted for their beneficial effects in treating FM. With further investigation, nano-carotenoids and particularly nano-lutein could potentially become an effective alternative treatment for patients with FM who do not respond to current treatment options.© 2023. The Author(s).