The transforming growth factor-beta (TGF-beta) plays a pivotal role in the pathophysiology of spinal cord injury (SCI) through its involvement in the formation of the glial scar. SCI triggers a cascade of cellular and molecular responses, where TGF-beta is upregulated and contributes to the activation and proliferation of astrocytes and other glial cells, leading to scar formation. This glial scar serves as both a physical and biochemical barrier to axonal regeneration, which complicates the recovery process. The dual role of TGF-beta in neuroprotection and inhibition of axonal growth presents a challenge for therapeutic strategies aimed at improving spinal cord repair. Various experimental approaches explored to modulate TGF-beta signaling in order to reduce glial scar formation while promoting neuronal regeneration. These include the use of TGF-beta inhibitors, gene therapy, and stem cell-based interventions. Despite significant advances, a comprehensive understanding which TGF-beta influences glial scar formation and SCI recovery is still evolving. This review aims to provide an in depth analysis of the current research on TGF-beta’s role in SCI, with a focus on its impact on glial scar formation and potential therapeutic approaches to mitigate its effects.