PURPOSE: Our study aims to summarize the current knowledge concerning the molecular pathway and mechanism responsible for the progress of orbitopathy in the thyroid. METHOD: A thorough investigation of the literature was conducted using Scopus, Elsevier, PubMed, ScienceDirect, and Web of Science databases, covering studies published between 2000 and 2024. The inclusion criteria focused on clinical trials, preclinical research, and ethnopharmacological studies that investigated the effects of traditional medicines on "orbitopathy in thyroid," "molecular pathway," "mechanism," "Medicinal Plants," "Mechanism of Action," and "Active Constituents." Studies were excluded if they lacked specific data on orbitopathy in thyroid, focused solely on orbitopathy in thyroid, or had inconclusive methodologies. RESULTS: Our findings indicate that TSHR autoantibodies drive orbital fibroblast activation, leading to inflammation, adipogenesis, and glycosaminoglycan accumulation. Elevated IL-17 and TNF-α levels contribute to immune dysregulation, while IGF-1R signaling enhances fibroblast proliferation and cytokine release. Biomarker analysis suggests that miR-146a, miR-155, and HLA-DR3 polymorphisms may serve as potential indicators for disease severity and progression. CONCLUSION: Early diagnostic markers and targeted therapies, including offer promising avenues for improved TAO management. A multidisciplinary, personalized approach integrating biomarker-driven treatment decisions may help optimize patient outcomes.