Reactive oxygen species (ROS) play an important 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 for improving the effectiveness of immunotherapies in infectious diseases, cancer, and autoimmune diseases. Moreover, ROS-responsive biomaterials can trigger the release of immunotherapeutics and provide tunable release kinetics, which can further boost their efficacy. This review will discuss 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. Finally, we will discuss the existing challenges and potential solutions for clinical translation of ROS-modulating and ROS-responsive approaches for immunotherapy, and provide an outlook for future research.