Objective To observe the efficacy and mechanism of Guizhi Fuling pill combined with dienogest in the treatment of endometriosis. Methods Sixty patients with blood stasis endometriosis, who visited the outpatient department of The Second Affiliated Hospital of Hunan University of Chinese Medicine from Jan. 2024 to May 2025, were randomly assigned to control group or treatment group, with 30 patients in each group. The control group received oral administration of dienogest, while the treatment group received Guizhi Fuling pill decoction in addition to dienogest. The total symptom score, traditional Chinese medicine (TCM) syndrome score, endometriosis health profile-5 (EHP-5) score and levels of transforming growth factor β1 (TGF-β1), interleukin 10 (IL-10), N-cadherin, vascular endothelial growth factor (VEGF), and carbohydrate antigen 125 (CA125) were compared between the 2 groups before treatment, 1 month after treatment, and 3 months after treatment. Results At 1 month after treatment, the total symptom score, TCM syndrome score, EHP-5 score and levels of TGF-β1, IL-10, N-cadherin, VEGF, and CA125 in the treatment group were significantly lower than those before treatment and in the control group (all P＜0.05). Moreover, all the above indexes in the treatment group remained significantly lower than those in the control group 3 months after treatment (all P＜0.05). Conclusion Guizhi Fuling pill combined with dienogest may alleviate pain and blood stasis symptoms in endometriosis patients and improve the quality of life by targeting the inflammation-epithelial-mesenchymal transition mechanism.