Curcumin, a natural compound derived from turmeric, exhibits potent immunomodulatory effects and has been studied for its therapeutic potential in rheumatoid arthritis (RA). RA is a systemic autoimmune disease characterized by synovial inflammation, cartilage destruction, and bone erosion. Macrophages, key immune cells involved in RA pathogenesis, exhibit two main phenotypes: M1 macrophages, which promote inflammation, and M2 macrophages, which suppress inflammation and aid tissue repair. An imbalance in the M1/M2 macrophage ratio is critical in RA progression. Curcumin modulates macrophage polarization, reducing proinflammatory cytokine production and promoting M2 macrophage differentiation, thereby alleviating RA symptoms. The mechanisms underlying curcumin's effects involve transcriptional regulation, epigenetic modifications, and metabolic reprogramming. Curcumin inhibits M1 macrophage polarization by suppressing NF-κB, AP-1, and STAT pathways, while promoting M2 macrophage polarization through the JAK-STAT pathway. It also suppresses macrophage migration, which may contribute to its anti-inflammatory effects. In animal models and clinical trials, curcumin has shown efficacy in reducing RA symptoms, improving disease activity scores, and enhancing inflammatory markers. Despite its promising therapeutic potential, challenges remain in determining optimal dosages and improving bioavailability. Further research is needed to fully elucidate curcumin's mechanisms of action and to develop effective strategies for RA treatment.Curcumin, a natural compound derived from turmeric, exhibits potent immunomodulatory effects and has been studied for its therapeutic potential in rheumatoid arthritis (RA). RA is a systemic autoimmune disease characterized by synovial inflammation, cartilage destruction, and bone erosion. Macrophages, key immune cells involved in RA pathogenesis, exhibit two main phenotypes: M1 macrophages, which promote inflammation, and M2 macrophages, which suppress inflammation and aid tissue repair. An imbalance in the M1/M2 macrophage ratio is critical in RA progression. Curcumin modulates macrophage polarization, reducing proinflammatory cytokine production and promoting M2 macrophage differentiation, thereby alleviating RA symptoms. The mechanisms underlying curcumin's effects involve transcriptional regulation, epigenetic modifications, and metabolic reprogramming. Curcumin inhibits M1 macrophage polarization by suppressing NF-κB, AP-1, and STAT pathways, while promoting M2 macrophage polarization through the JAK-STAT pathway. It also suppresses macrophage migration, which may contribute to its anti-inflammatory effects. In animal models and clinical trials, curcumin has shown efficacy in reducing RA symptoms, improving disease activity scores, and enhancing inflammatory markers. Despite its promising therapeutic potential, challenges remain in determining optimal dosages and improving bioavailability. Further research is needed to fully elucidate curcumin's mechanisms of action and to develop effective strategies for RA treatment.