Objective To investigate the potential active ingredients of the Rhodiola rosea-Euonymus alatus medicine (“Tianyu” medicine) in combating rheumatoid arthritis (RA) and its regulatory effect on the Keap1/Nrf2/HO-1 signaling pathway in oxidative stress. Methods UPLC-MS/MS was employed to detect the blood components of the "Tianyu" medicine. A collagen-induced arthritis (CIA) rat model was established, and the efficacy of "Tianyu" medicine on RA was evaluated by observing joint swelling, arthritis scores, and thymus and spleen indices. The effects of "Tianyu" medicine on oxidative stress-related indicators in CIA rats were assessed by measuring the serum levels of SOD, CAT, GSH-Px, and MDA using ELISA. Western blot and qPCR techniques were used to explore the impact of "Tianyu" medicine on the protein and mRNA expression of Keap1/Nrf2/HO-1 pathways in the synovial tissue of rats. Results The blood components of "Tianyu" medicine included 43 compounds, mainly alkaloids, steroids, and terpenoids, followed by organic acids, hormones, and phenolic compounds. In vivo experiments showed that compared to the control group, rats in the model group exhibited inflammation and oxidative stress. Compared to the model group, rats in the "Tianyu" treatment group had significantly reduced joint swelling, arthritis scores, and thymus and spleen indices. Additionally, the levels of SOD, GSH-Px, and CAT in the serum were significantly increased, while MDA levels decreased (P<0.05). Keap1 expression was downregulated (P<0.01), and the expression of Nrf2 and HO-1 in the nucleus was upregulated (P<0.05).Conclusion The "Tianyu" medicine regulates the Keap1/Nrf2/HO-1 signaling pathway, inhibits oxidative stress, and alleviates the pathological progression of RA.