ROS plays a critical role in the secondary injury process of spinal cord injury (SCI), contributing to inflammation and various forms of regulated cell death, including apoptosis, autophagy, pyroptosis, and ferroptosis. The transcription factor Nrf2 is a key regulator of cellular redox balance and is involved in the response to oxidative stress. Recent research highlights the interaction between ROS and the regulation of different modes of neuronal cell death after SCI. Additionally, materials science approaches, such as exosomes, hydrogels, and nanomaterials, are being explored to modulate ROS production and clearance, thereby alleviating SCI. The review discusses the mechanisms by which ROS contribute to cell death pathways and the potential of targeting ROS to reduce neuronal damage. It also explores the role of Nrf2 in regulating ROS and the potential of antioxidants and exosome-based therapies in mitigating oxidative stress and cell death in SCI. The study emphasizes the importance of controlling ROS levels to improve outcomes in SCI patients.ROS plays a critical role in the secondary injury process of spinal cord injury (SCI), contributing to inflammation and various forms of regulated cell death, including apoptosis, autophagy, pyroptosis, and ferroptosis. The transcription factor Nrf2 is a key regulator of cellular redox balance and is involved in the response to oxidative stress. Recent research highlights the interaction between ROS and the regulation of different modes of neuronal cell death after SCI. Additionally, materials science approaches, such as exosomes, hydrogels, and nanomaterials, are being explored to modulate ROS production and clearance, thereby alleviating SCI. The review discusses the mechanisms by which ROS contribute to cell death pathways and the potential of targeting ROS to reduce neuronal damage. It also explores the role of Nrf2 in regulating ROS and the potential of antioxidants and exosome-based therapies in mitigating oxidative stress and cell death in SCI. The study emphasizes the importance of controlling ROS levels to improve outcomes in SCI patients.