<p>Reactive oxygen species (ROS) induce inflammation, senescence and various forms of cell death in nucleus pulposus cells. By promoting these reactions and their interplay, ROS significantly accelerate intervertebral disc degeneration (IDD). Conventional surgical interventions and analgesics can alleviate symptoms but fail to halt the disease progression mechanistically. Eliminating ROS may serve as a fundamental therapeutic approach to mitigate IDD. Within the endogenous antioxidant defense system for scavenging ROS, superoxide dismutase (SOD) serves as the first line of defense, playing an irreplaceable role in initiating the clearance of reactive species. Furthermore, transcriptomics and single-cell sequencing analyses have identified SOD as a key gene in nucleus pulposus tissue degeneration, underscoring its unique value in the research of antioxidant therapies for IDD. Recently, a range of SOD-centered therapeutic strategies, including the enhancement of endogenous SOD via drugs, hormones, herbal medicines, exosomes, genetically engineered stem cells, in addition to the use of exogenous SOD nanozymes have been explored. Despite these advancements, a comprehensive overview of these emerging approaches remains elusive. This review details how ROS contribute to IDD and critically assesses current and future SOD-centered therapeutic strategies, providing valuable insights for clinical practice and research directions.</p> Graphical Abstract <p></p>