This review discusses the immunomodulatory effects of curcumin on macrophage polarization in rheumatoid arthritis (RA). RA is a systemic autoimmune disease characterized by synovial inflammation, cartilage destruction, and bone erosion. Macrophages play a crucial role in RA pathogenesis, with an imbalance in the M1/M2 macrophage ratio being critical. Curcumin, a natural compound derived from turmeric, has been shown to modulate macrophage polarization and function, thereby alleviating inflammation. The review highlights the following key points: 1. **Macrophage Polarization in RA**: Macrophages can be polarized into M1 and M2 phenotypes. M1 macrophages exacerbate inflammation by producing proinflammatory cytokines and chemokines, while M2 macrophages inhibit inflammation and promote tissue repair. An imbalance in the M1/M2 ratio is a key factor in RA progression. 2. **Mechanisms of Curcumin's Action**: Curcumin modulates macrophage polarization through various mechanisms, including transcriptional regulation, epigenetic modulation, and metabolic reprogramming. It inhibits the activation of transcription factors such as NF-κB, STAT family, and HIFs, which are involved in M1 macrophage polarization. Curcumin also affects epigenetic modifications like DNA methylation and RNA methylation, and regulates metabolic pathways. 3. **Therapeutic Effects of Curcumin**: Curcumin has been shown to improve symptoms and reduce inflammation in RA patients through its ability to inhibit proinflammatory cytokines produced by M1 macrophages, promote M2 macrophage differentiation, and suppress macrophage migration. Clinical trials have demonstrated the efficacy and safety of curcumin in treating RA, with no significant side effects reported. 4. **Future Directions**: Despite the promising results, challenges remain in optimizing curcumin's clinical application, such as determining the optimal dosage and enhancing its bioavailability. Further research is needed to fully understand the underlying mechanisms and to explore the potential of curcumin in RA treatment. The review provides a comprehensive overview of the role of curcumin in modulating macrophage polarization and its therapeutic potential in RA, emphasizing the need for further studies to refine its use in clinical settings.This review discusses the immunomodulatory effects of curcumin on macrophage polarization in rheumatoid arthritis (RA). RA is a systemic autoimmune disease characterized by synovial inflammation, cartilage destruction, and bone erosion. Macrophages play a crucial role in RA pathogenesis, with an imbalance in the M1/M2 macrophage ratio being critical. Curcumin, a natural compound derived from turmeric, has been shown to modulate macrophage polarization and function, thereby alleviating inflammation. The review highlights the following key points: 1. **Macrophage Polarization in RA**: Macrophages can be polarized into M1 and M2 phenotypes. M1 macrophages exacerbate inflammation by producing proinflammatory cytokines and chemokines, while M2 macrophages inhibit inflammation and promote tissue repair. An imbalance in the M1/M2 ratio is a key factor in RA progression. 2. **Mechanisms of Curcumin's Action**: Curcumin modulates macrophage polarization through various mechanisms, including transcriptional regulation, epigenetic modulation, and metabolic reprogramming. It inhibits the activation of transcription factors such as NF-κB, STAT family, and HIFs, which are involved in M1 macrophage polarization. Curcumin also affects epigenetic modifications like DNA methylation and RNA methylation, and regulates metabolic pathways. 3. **Therapeutic Effects of Curcumin**: Curcumin has been shown to improve symptoms and reduce inflammation in RA patients through its ability to inhibit proinflammatory cytokines produced by M1 macrophages, promote M2 macrophage differentiation, and suppress macrophage migration. Clinical trials have demonstrated the efficacy and safety of curcumin in treating RA, with no significant side effects reported. 4. **Future Directions**: Despite the promising results, challenges remain in optimizing curcumin's clinical application, such as determining the optimal dosage and enhancing its bioavailability. Further research is needed to fully understand the underlying mechanisms and to explore the potential of curcumin in RA treatment. The review provides a comprehensive overview of the role of curcumin in modulating macrophage polarization and its therapeutic potential in RA, emphasizing the need for further studies to refine its use in clinical settings.