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Reactive oxygen species (ROS), acting as essential mediators in the biological system, highly influence the physiologic and pathologic processes of the human body. The aberrant production of ROS, caused by various diseases, may lead to inflammation and cellular damages, as well as homeostasis disruption. In recent years, biomaterials sensitive to biological stimuli have received increasing attention due to their potential for achieving more specific diagnoses and effective treatments. Particularly, ROS-responsive biomaterials could be triggered by ROS in the damaged tissue microenvironment to release their payloads or exert a therapeutically beneficial effect, consequently regulating the elevated ROS level and downregulating the oxidative stress to promote tissue regeneration. In this review, we outline the underlying mechanisms of ROS generation in the tissue microenvironment of various diseases and summarize the cutting-edge advances in developing ROS-responsive biomaterials to expedite inflammation-related diseases, regenerative medicine and tissue engineering applications in various body systems. In particular, we pointed out the challenges and shortcomings that the current ROS-sensitive materials encounter, offer distinctive insights into the field and present solutions or improved strategies. [ABSTRACT FROM AUTHOR]