Introduction: Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disease. Guogong Jiu (GGJ) is a classical traditional Chinese medicine formula that is widely used in clinical treatment of rheumatoid arthritis. Nevertheless, the gut microbiota and meta-bolic mechanisms have not been fully studied. The objective of this study was to elucidate the gut microbiota-mediated mechanisms by which GGJ alleviates RA using network phar-macology, metabolomics, and experimental approaches. Methods: A rat model of collagen-induced arthritis was established to assess anti-arthritic effects systemically. The arthritis index, histopathology, inflammatory cytokines, and gut mi-crobiota analysis (16S rRNA) were assessed for their effects. The serum and fecal metabo-lomics were done using UHPLC-Q-Exactive MS/MS. Moreover, network pharmacology and secondary metabolome analysis were used to identify the active herbal components, potential targets, and pathways, which were validated in Rheumatoid Arthritis Fibroblast-Like Syno-viocytes (RA-FLS) as well. Results: GGJ improved the symptoms of Rheumatoid arthritis. GGJ affected pathways in-volved in amino acid, lipid, and energy metabolism. Moreover, the assessment of gut micro-biota revealed that GGJ helped restore microbial equilibrium by augmenting beneficial bac-teria populations, including Lactobacillus and Alloprevotella, alongside diminishing Prevotella abundance. An integrated analysis identified NF-κB, MAPK, and NRF2 as key targets, which were subsequently validated at the cellular level. Discussion: The multi-omics integration reveals that GGJ exerts its therapeutic effects through coordinated regulation of the gut-joint axis, involving microbiota restoration, meta-bolic reprogramming, and signaling pathways. These findings provide a mechanistic basis for the clinical application of GGJ in RA. Conclusion: GGJ is effective in RA through multi-target effects involving modulation of inflammatory signaling pathways, mediation of metabolic reprogramming, and restoration of gut microbiota. The clinical application of GGJ for RA is therefore scientifically supported.