Chemotherapy is a common treatment for cancer, but it often causes severe side effects. Recent research suggests that chemotherapy toxicity is not solely due to direct cell death but is also caused by cell-free chromatin particles (cfChPs) released from dying cells. These particles can enter healthy cells and cause DNA damage and inflammation, leading to prolonged toxicity. Studies show that deactivating cfChPs can reduce chemotherapy toxicity. Resveratrol and copper (R-Cu) have been identified as effective agents for deactivating cfChPs. R-Cu is easily administered orally and has low toxicity, making it a promising treatment for human use. Laboratory and clinical studies indicate that R-Cu can significantly reduce chemotherapy-related toxicities, including mucositis, neutropenia, and other severe side effects. Additionally, R-Cu may have therapeutic effects on tumor cells by deactivating intratumoral cfChPs. The findings suggest that targeting cfChPs could be a new approach to reduce chemotherapy toxicity and improve patient outcomes. Further research is needed to confirm these findings and understand the full potential of R-Cu in clinical practice.Chemotherapy is a common treatment for cancer, but it often causes severe side effects. Recent research suggests that chemotherapy toxicity is not solely due to direct cell death but is also caused by cell-free chromatin particles (cfChPs) released from dying cells. These particles can enter healthy cells and cause DNA damage and inflammation, leading to prolonged toxicity. Studies show that deactivating cfChPs can reduce chemotherapy toxicity. Resveratrol and copper (R-Cu) have been identified as effective agents for deactivating cfChPs. R-Cu is easily administered orally and has low toxicity, making it a promising treatment for human use. Laboratory and clinical studies indicate that R-Cu can significantly reduce chemotherapy-related toxicities, including mucositis, neutropenia, and other severe side effects. Additionally, R-Cu may have therapeutic effects on tumor cells by deactivating intratumoral cfChPs. The findings suggest that targeting cfChPs could be a new approach to reduce chemotherapy toxicity and improve patient outcomes. Further research is needed to confirm these findings and understand the full potential of R-Cu in clinical practice.