To reveal the molecular mechanism of Siegesbeckia orientalis L. in treating rheumatoid arthritis (RA), core targets were screened out through the random forest (RF) model on the datasets GSE100191 and GSE17755. Perform single sample gene set enrichment analysis (ssGSEA) on core targets. The chemical composition of Siegesbeckia orientalis L. was downloaded from the TCMSP database, and the optimization of compounds was based on SYBYL2.1.1 energy minimization. Molecular docking analysis was used to investigate the binding of Siegesbeckia orientalis L. compounds to YTHDC1 and IGFBP2 genes. The results were analyzed by total score(T_Score) as the threshold. The results show these as follows. The constructed RF model was used to Insulin-like growth factor binding protein 2 (IGFBP2), YTH N6-methyladenosine RNA binding protein C1(YTHDC1), AlkB Homolog 5 (ALKBH5), insulin like growth factor 2 MRNA binding protein 1(IGFBP2), with IGFBP2 being the most significant gene, followed by YTHDC1, ALKBH5, and IGF2BP1. Compared with the normal control group, ALKBH5, YTHDC1, IGFBP2, and IGF2BP1 were highly expressed in RA, with significant differences (P < 0.05). The IGFBP2 gene is associated with various immune cells, and an increase in IGFBP2 expression leads to a significant increase in the number of multiple immune cells, resulting in a microenvironment of immune overactivation. Through molecular docking, 31 compounds of Siegesbeckia orientalis L. were discovered, with 14 compounds showing good binding to IGFBP2 and 12 compounds showing good binding to YTHDC1. Among them, darutoside is the key substance basis for treating RA. It can be seen that the mechanism of action of Siegesbeckia orientalis L. in treating RA may be related to the immune system, inhibiting immune overactivation and preventing the occurrence of inflammatory storms.