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Objective: The main objective was to assess the therapeutic efficacy of selenium alone versus a combination of myo-inositol and selenium (MI + Se) in treating patients with autoimmune thyroiditis (AIT). The study aims to determine which treatment option is more effective in restoring euthyroid state, as indicated by changes in thyroid-stimulating hormone (TSH), T3, T4, thyroid peroxidase antibodies (TPOAb), and thyroglobulin antibodies (TgAb) Methods: Google Scholar and PubMed databases were searched for randomized controlled trials (RCTs) and observational studies that reported outcomes of combined treatment (MI + Se) in restoring a euthyroid state, specifically comparing it with selenium-only (Se-only) treatment. Changes in TSH, T3, T4, TPOAb, and TgAb levels from baseline were defined as indicators to compare the effect of combined versus selenium-only treatment in restoring euthyroid levels. The Cochrane risk of bias tool and Newcastle Ottawa Scale were used to assess the quality of the randomized control trials included in the study. Review Manager (version 5.4, Nordic Cochrane Centre, Copenhagen, Denmark) was used for statistical analysis. Result: We pooled three studies, enrolling 151 participants in the MI + Se group and 137 participants in the Se group. Supplementation of Se with MI demonstrated a significant reduction in TSH levels compared to Se alone (SMD = −1.15, 95% CI: −1.60 to −0.69, P <.00001). MI + Se treatment also significantly reduced TgAb levels compared to Se (SMD = −0.51, 95% CI: −0.78 to −0.24, P =.0002). In contrast, TPOAB, T3 and T4 levels were non-significantly reduced from baseline in patients treated with MI + Se when compared to Se alone (SMD = −0.81, 95% CI: −0.44 to 0.09, P =.20), (SMD = 0.16, 95% CI: −0.09 to 0.42, P =.22), and (SMD = 0.30, 95% CI: −0.23 to 0.83, P =.26) respectively. Conclusion: Supplementation of Se with MI showed a significant reduction in TSH and TgAb levels compared to selenium-only treatment, with a non-significant reduction in TPOAB, T3, and T4 levels. This entails the need for powered clinical trials and observational studies with longer follow-ups to critically assess the role of combined therapy in restoring euthyroid state in patients with AIT. Plain Language Summary: Summary of Role of Supplementation with Selenium and Myo-inositol vs. Selenium alone in patients of Autoimmune Thyroiditis The study aimed to determine whether taking the supplementation therapy of myo-inositol and selenium (MI+Se) together is more effective than taking selenium alone for people suffering from autoimmune thyroiditis, a condition in which the immune system attacks the thyroid gland and often leads to hypothyroidism. Researchers reviewed relevant studies from Google Scholar and PubMed, focusing on randomized control trials (RCTs) and observational studies that compared the effects of selenium alone versus selenium plus myo-inositol. They analyzed changes in thyroid-related blood markers TSH, T3, T4, TPOAb, and TgAb levels) to assess effectiveness of the given therapy. The study included three RCTs with 288 participants that were assessed through the supplementation therapy of selenium alone and myo-inositol plus selenium (MI+Se). Findings suggest that the combination of selenium and myo-inositol significantly reduced TSH levels, which indicates thyroid activity and improvement in the condition, more than selenium alone. It also lowered TgAb levels, antibodies that attack the thyroid, more effectively than selenium alone. However, the two groups had no significant changes in other markers like TPOAb, T3, and T4. The results suggest that the combination treatment might be more effective in reducing harmful antibodies and improving thyroid function compared to selenium alone. This finding is particularly relevant for managing AIT and improving thyroid health, pointing to potentially better treatment strategies. Nevertheless, the study emphasizes the need for more extensive and longer-term research to confirm these benefits and fully understand the implications. This research highlights the promise of combining supplementation with selenium and myo-inositol as a more effective approach for people with autoimmune thyroiditis (AIT). This could lead to improved management and outcomes for this common thyroid condition. [ABSTRACT FROM AUTHOR]