Degenerative cervical myelopathy (DCM) is a challenging neurological disorder characterized by chronic spinal cord compression, and surgical decompression is the only established treatment to relieve this compression. However, post-decompression spinal cord ischemia-reperfusion (IR) injury paradoxically worsens neurological function, and effective therapeutic treatments remain lacking. In this study, we purified a homogeneous and structurally well-defined Astragalus polysaccharide (APS) from Astragali Radix through sequential water extraction, alcohol precipitation, ion-exchange, and gel-filtration chromatography. Structural analysis revealed that this APS is a unique, low-molecular-weight, branched neutral polysaccharide with a (1 → 4)-α-D-glucan backbone. In a decompressive DCM rat model, 28 days of APS gavage improved motor function recovery (BBB scale and inclined plane test) in a dose-dependent manner, increased neuronal survival, reduced cavity area, and modulated apoptosis and ferroptosis without systemic toxicity. Mechanistically, as indicated by single-nucleus RNA sequencing and metabolomic profiling of rats, APS exerts neuroprotective effects by activating the neuronal Nrf2/HO-1 pathway, enhancing oxidative phosphorylation, subsequently inhibiting ferroptosis and apoptosis, and enhancing the tricarboxylic acid (TCA) cycle. In vivo, APS reduces ROS accumulation, enhances oxidative phosphorylation, upregulates the Nrf2/HO-1 pathway, and protects mitochondrial ultrastructure. In vitro, APS increases ATP production, restores mitochondrial membrane potential, and upregulates HO-1 expression, and the causal role of Nrf2 was demonstrated by Nrf2 knockdown or ML385 inhibition abolished APS-induced protection. This study systematically reveals the structure-activity relationship of this well-defined APS and its underlying molecular mechanisms, supporting its translational development as a candidate drug for spinal cord IR injury and providing a research paradigm for natural product-based investigations.