Spinal cord injury (SCI) often leads to significant neurological impairment and poses a substantial therapeutic challenge, with disulfidptosis recently identified as a potential mechanism exacerbating such pathologies. This study sought to elucidate the role of Bisphenol A (BPA) in modulating key genes and metabolites associated with disulfidptosis in the context of SCI. Utilizing a murine SCI model, we established three cohorts: a sham control, an SCI group, and an SCI group treated with BPA. Comprehensive assessments, including locomotor recovery via the Basso Mouse Scale (BMS), gait analysis, histopathological evaluations through H&E and Nissl staining, and integrated transcriptomic and metabolomic profiling, were conducted. Results revealed that BPA administration significantly improved locomotor recovery and mitigated histopathological alterations, with Ndufs1, Ndufa11, and Ndufb10 identified as pivotal genes, alongside leukotriene B4 (LTB4) and prostaglandin B2 (PGB2) as crucial metabolites. Notably, these genes were intricately linked to the oxidative phosphorylation (OXPHOS) pathway and exhibited positive intercorrelations, while the metabolites were enriched within the arachidonic acid (AA) metabolism pathway. As the injury progressed, key gene expression diminished, whereas metabolite concentrations increased; BPA treatment effectively reversed these trends. Collectively, these findings indicate that BPA exerts a protective effect against SCI by disrupting a harmful feedback loop involving mitochondrial dysfunction and inflammatory activation, thus countering disulfidptosis and fostering an environment conducive to neural regeneration, underscoring its potential as a therapeutic agent in SCI management.