Duhuo-Jisheng-Tang is a Chinese herbal formula designed to treat rheumatoid arthritis (RA) with syndrome dual deficiency of liver and kidney. Although its therapeutic clinical effect is widely accepted over one thousand years, its therapeutic agents are still obscure. In this study, we explored the potential therapeutic agents of Duhuo-Jisheng-Tang for RA by integrating leading knowledge databases of different biomedical domains. The molecule mechanism includes compositional herbal medicine, chemical compound, target protein, RA OMIM genes, FDA approved RA drug targets, and pathways. As a result, Duhuo-Jisheng-Tang's 11 target proteins can be found in RA's OMIM genes (e.g., UGT1, UGT1A9, GNT1, and JAK3) and FDA approved RA drug targets (e.g., CMKBR2/5, CCR2/5, APRF, and STAT1/3). What's more, these 11 genes/proteins are mainly enriched in pathways of disease, immune system, signal transduction, and metabolism. It demonstrates that Duhuo-Jisheng-Tang may regulate a wide range of different systems associated with RA which might indicate that Chinese herbal formula's therapeutic effects are demonstrated through system-level regulation rather than targeting disease specified genes/proteins.