Excessive reactive oxygen species (ROS) in nucleus pulposus cells (NPCs) promote extracellular matrix (ECM) degradation and cellular inflammatory responses by activating a variety of cellular pathways, ultimately inducing cell apoptosis and leading to the development of low back pain. Here, we designed and fabricated an isoginkgetin-loaded ROS-responsive delivery system (IGK@SeNP) based on diselenide block copolymers. Successfully encapsulated IGK was released intelligently and rapidly in a microenvironment with high ROS levels in degenerative disc. Controlled-release IGK not only efficiently scavenged ROS from the intervertebral disc together with diselenide block copolymers but also effectively enhanced autophagy in NPCs to inhibit ECM degradation and cell apoptosis, and showed significant therapeutic effects in the rat intervertebral disc degeneration (IDD) model. Overall, the synergistic effects of IGK@SeNP in ROS scavenging and autophagy enhancement endowed it with an attractive therapeutic strategy for IDD treatment.