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Rheumatoid arthritis (RA) is a debilitating autoimmune disease that severely affects patients' quality of life. Growing evidence links the gut microbiota, metabolism, and immune regulation to RA, driving interest in gut-targeted therapies. This study evaluates the therapeutic potential of Lactiplantibacillus plantarum-fermented hemp seeds (FHS) in collagen-induced arthritis (CIA) mouse models. FHS intervention significantly reduced joint swelling, cartilage and synovial damage, and systemic inflammation while restoring mobility and balancing CD4+ T cell differentiation. Compared to L. plantarum alone, FHS demonstrated superior efficacy. Additionally, FHS modulated RA-associated gut bacteria, including Clostridium disporicum, Duncaniella dubosii, Eisenbergiella massiliensis, Waltera intestinalis, and Muribaculum gordoncarteri, while restoring RA-suppressed species like Akkermansia muciniphila, Konateibacter massiliensis, Lactobacillus johnsonii, Ruminococcus champanellensis, and Phocaeicola vulgatus. FHS also influenced key metabolites, such as short-chain fatty acids, stearic acid, oleic acid, taurine, palmitic acid, docosahexaenoic acid, linoleic acid, and L-tyrosine, impacting metabolic pathways linked to RA progression. Notably, indolelactic acid, homovanillic acid, and bioactive peptides in FHS were absorbed into the bloodstream, exerting direct anti-inflammatory effects. These findings underscore FHS's potential as a therapeutic functional ingredient for RA, offering insights into its mechanisms through gut microbiota modulation and metabolic regulation.