**Background:** Thyroid-associated orbitopathy (TAO), also known as Graves' orbitopathy, is an orbital inflammatory disorder linked to autoimmune thyroid disease, primarily Graves' disease. It is characterized by soft tissue inflammation, eyelid retraction, diplopia, proptosis, and sight-threatening complications. Orbital fibroblasts (OF) are central to TAO pathogenesis, driving inflammation, hyaluronan overproduction, adipogenesis, fibrosis, oxidative stress, and autophagy. Current treatments have limitations in response rates, toxicity, and accessibility, prompting the search for novel therapies. Traditional Chinese medicine (TCM) active ingredients have shown potential in pre-clinical studies.
**Key Results:** Eleven TCM compounds demonstrated inhibition of TAO-OF in vitro, and three (polydatin, curcumin, gypenosides) showed improvement in TAO mouse models. Tanshinone IIA reduced inflammation (IL-6, IL-8, MCP-1), oxidative stress (ROS, HO-1), and adipogenesis (PPARγ, C/EBPα). Resveratrol and polydatin displayed anti-oxidative and anti-adipogenic properties; polydatin reduced ROS via Keap1/NRF2/ARE pathway and inhibited adipose expansion in mice. Celastrol inhibited IL-1β-induced pro-inflammatory molecules (IL-6, IL-8, PGE2, COX-2, ICAM-1) via NF-κB pathway. Triptolide prevented TAO-OF activation (HLA-DR, ICAM-1, CD40, HA synthesis). Icariin inhibited autophagy and adipogenesis via AMPK/mTOR signaling in vitro and in vivo. Astragaloside IV reduced inflammation via suppressing autophagy, and inhibited fat accumulation and collagen deposition in TAO mice. Curcumin displayed anti-inflammatory, anti-oxidative, anti-adipogenic, anti-fibrotic, and anti-angiogenic effects via multiple pathways (ERK, JNK, NF-κB, β-catenin, SMAD2/3). Gypenosides reduced inflammation (TLR4/NF-κB), oxidative stress (NRF2/ERK/HO-1), fibrosis (SMAD2/4), and oxidative stress-mediated autophagy and apoptosis. Dihydroartemisinin inhibited OF proliferation, inflammation (IL-6, IL-8, CXCL-1, MCP-1, ICAM-1), HA production, and fibrosis (α-SMA, CTGF) via ERK and STAT3 pathways. Berberine attenuated inflammation (IL-6, PTX-3, COX-2 via NF-κB), HA production, adipogenesis (AMPK, PPARγ), and fibrosis.
**Clinical Implications:** The reviewed TCM compounds target multiple pathological processes in TAO, offering potential as novel therapeutic agents. However, evidence is limited to pre-clinical studies. Clinical trials of different phases with adequate power and sound methodology are warranted to evaluate appropriate dosage, safety, and efficacy in TAO management. The growing integration of conventional Western medicine and TCM may help identify effective molecules and define their clinical role.