Reactive oxygen species (ROS) play a critical role in regulating the immune system by affecting pathogens, cancer cells, and immune cells. Recent advances in biomaterials have enabled precise modulation of ROS levels in target tissues to improve the effectiveness of immunotherapies for infectious diseases, cancer, and autoimmune diseases. ROS-responsive biomaterials can trigger the release of immunotherapeutics and provide tunable release kinetics, enhancing their efficacy. This review discusses the latest biomaterial-based approaches for both precise modulation of ROS levels and using ROS as a stimulus to control the release kinetics of immunotherapeutics. It also addresses the challenges and potential solutions for clinical translation of ROS-modulating and ROS-responsive approaches for immunotherapy, and provides an outlook for future research. ROS can be used to kill pathogens by generating ROS in response to infections, such as viral or bacterial infections. ROS can also be used to inactivate viruses for vaccine production, as shown by studies on H2O2 inactivating viruses like LCMV. ROS can be used to kill cancer cells by generating ROS in response to stimuli such as laser, ultrasound, or ionizing radiation. Photodynamic therapy (PDT) uses photosensitizers and lasers to generate ROS, which can kill cancer cells and induce immunogenic cell death. Sonodynamic therapy (SDT) uses sonosensitizers and ultrasound to generate ROS, which can also kill cancer cells and induce immunogenic cell death. Both PDT and SDT have shown promise in treating various cancers. ROS can be used to activate antigen-presenting cells (APCs) such as dendritic cells (DCs) and macrophages. ROS can enhance the maturation and antigen-presenting ability of DCs, leading to stronger immune responses. ROS can also polarize macrophages toward the antitumor M1 phenotype, enhancing antitumor immunity. ROS can be used to activate T cells by modulating their function and enhancing their ability to recognize and kill tumor cells. ROS can also be used to modulate the immune response in autoimmune and inflammatory diseases by scavenging ROS to reduce inflammation and promote tissue repair. ROS-responsive biomaterials can be used to tune drug delivery for immunotherapy by releasing drugs in response to elevated ROS levels in the tumor microenvironment. These materials can be used to deliver immunotherapeutics to the target site, enhancing their efficacy. ROS-responsive biomaterials can also be used to deliver immunosuppressive agents to DCs to treat autoimmune diseases. These materials can be used to modulate the immune response in complex diseases such as immuno-related, cancerous, and metabolic disorders. Challenges in clinical translation include achieving spatiotemporal control of ROS, understanding the mechanism of action of ROS, and ensuring the safety and efficacy of ROS-modulating and ROS-responsive approaches. Further research is needed to develop novel sensitizers with reduced cytotoxicity, improved drug stability, and high quantum yield. Additionally, further studies areReactive oxygen species (ROS) play a critical role in regulating the immune system by affecting pathogens, cancer cells, and immune cells. Recent advances in biomaterials have enabled precise modulation of ROS levels in target tissues to improve the effectiveness of immunotherapies for infectious diseases, cancer, and autoimmune diseases. ROS-responsive biomaterials can trigger the release of immunotherapeutics and provide tunable release kinetics, enhancing their efficacy. This review discusses the latest biomaterial-based approaches for both precise modulation of ROS levels and using ROS as a stimulus to control the release kinetics of immunotherapeutics. It also addresses the challenges and potential solutions for clinical translation of ROS-modulating and ROS-responsive approaches for immunotherapy, and provides an outlook for future research. ROS can be used to kill pathogens by generating ROS in response to infections, such as viral or bacterial infections. ROS can also be used to inactivate viruses for vaccine production, as shown by studies on H2O2 inactivating viruses like LCMV. ROS can be used to kill cancer cells by generating ROS in response to stimuli such as laser, ultrasound, or ionizing radiation. Photodynamic therapy (PDT) uses photosensitizers and lasers to generate ROS, which can kill cancer cells and induce immunogenic cell death. Sonodynamic therapy (SDT) uses sonosensitizers and ultrasound to generate ROS, which can also kill cancer cells and induce immunogenic cell death. Both PDT and SDT have shown promise in treating various cancers. ROS can be used to activate antigen-presenting cells (APCs) such as dendritic cells (DCs) and macrophages. ROS can enhance the maturation and antigen-presenting ability of DCs, leading to stronger immune responses. ROS can also polarize macrophages toward the antitumor M1 phenotype, enhancing antitumor immunity. ROS can be used to activate T cells by modulating their function and enhancing their ability to recognize and kill tumor cells. ROS can also be used to modulate the immune response in autoimmune and inflammatory diseases by scavenging ROS to reduce inflammation and promote tissue repair. ROS-responsive biomaterials can be used to tune drug delivery for immunotherapy by releasing drugs in response to elevated ROS levels in the tumor microenvironment. These materials can be used to deliver immunotherapeutics to the target site, enhancing their efficacy. ROS-responsive biomaterials can also be used to deliver immunosuppressive agents to DCs to treat autoimmune diseases. These materials can be used to modulate the immune response in complex diseases such as immuno-related, cancerous, and metabolic disorders. Challenges in clinical translation include achieving spatiotemporal control of ROS, understanding the mechanism of action of ROS, and ensuring the safety and efficacy of ROS-modulating and ROS-responsive approaches. Further research is needed to develop novel sensitizers with reduced cytotoxicity, improved drug stability, and high quantum yield. Additionally, further studies are