Reactive oxygen species (ROS) play a crucial role in regulating the immune system by affecting pathogens, cancer cells, and immune cells. Recent advances in biomaterials have leveraged this mechanism to precisely modulate ROS levels in target tissues, enhancing 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, further boosting their efficacy. This review discusses the latest biomaterial-based approaches for precise ROS modulation and using ROS as a stimulus to control drug release kinetics in immunotherapy. It also addresses the challenges and potential solutions for clinical translation of ROS-modulating and ROS-responsive approaches, providing an outlook for future research. The review covers ROS-modulating strategies to fight pathogens, cancer, and autoimmune diseases, as well as ROS-responsive biomaterials for drug delivery and immune regulation.Reactive oxygen species (ROS) play a crucial role in regulating the immune system by affecting pathogens, cancer cells, and immune cells. Recent advances in biomaterials have leveraged this mechanism to precisely modulate ROS levels in target tissues, enhancing 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, further boosting their efficacy. This review discusses the latest biomaterial-based approaches for precise ROS modulation and using ROS as a stimulus to control drug release kinetics in immunotherapy. It also addresses the challenges and potential solutions for clinical translation of ROS-modulating and ROS-responsive approaches, providing an outlook for future research. The review covers ROS-modulating strategies to fight pathogens, cancer, and autoimmune diseases, as well as ROS-responsive biomaterials for drug delivery and immune regulation.