Abstract:Rheumatoid arthritis (RA) is a highly teratogenic autoimmune disease that remains incurable. The abnormal proliferation and invasion of fibroblast-like synoviocytes (FLS) are the core processes of joint destruction in RA. Mitochondrial apoptosis, as an endogenous apoptotic pathway, can regulate the growth, proliferation and metabolism of RA-FLS and has become an important therapeutic target for RA. Although modern medicine can alleviate symptoms and delay the progression of the disease to some extent, it is difficult to meet the long-term treatment needs of patients due to significant adverse reactions. Traditional Chinese medicine, based on syndrome differentiation and the concept of holistic treatment, demonstrates unique advantages in multi-target regulation in the treatment of RA. Studies have found that active components of traditional Chinese medicine such as flavonoids, saponins, and alkaloids, as well as traditional Chinese medicine formulas like Duhuo Jisheng Decoction, Danggui Niandong Decoction, and Guizhi Shaoyao Zhimu Decoction, can regulate pathways such as NF-κB, JAK2/STAT3, and PI3K/Akt, and possibly through the mitochondrial pathway, induce apoptosis of RA-FLS, and in concert reduce inflammatory responses, inhibit proliferation and invasion, suppress autophagy, inhibit pyroptosis, inhibit angiogenesis, and arrest the cell cycle, ultimately exerting anti-RA effects. This article reviews the relevant research in recent years to systematically expound the mechanism of traditional Chinese medicine in regulating FLS mitochondrial apoptosis to treat RA, with the aim of providing new ideas for clinical treatment.