Biomaterial-based regenerative strategies for spinal cord injury (SCI) aim to repair the spinal cord by leveraging biomaterials, which can serve as scaffolds, drug delivery vehicles, or artificial bioactive niches. This review summarizes representative biomaterials, including natural, synthetic, nano, and hybrid materials, and their applications in SCI treatment. It also discusses advanced tissue engineering fabrication techniques and biomaterial-based therapeutic strategies to reduce secondary damage and promote repair. The review highlights clinical studies on functional bioscaffolds and provides insights for future research in spinal cord regeneration. Spinal cord injury leads to permanent neurological impairment due to complex pathological mechanisms and a unique post-injury microenvironment. Current treatments lack effectiveness in promoting SCI recovery. Tissue engineering has introduced new approaches using biomaterials to create favorable microenvironments for nerve regeneration. Biomaterials can be tailored to interact with the nervous system, providing spatial scaffolds, drug delivery, and artificial bioactive niches resembling the extracellular matrix. Natural materials such as collagen, fibrin, hyaluronic acid, chitosan, and alginate are used for their biocompatibility, biodegradability, and ability to support tissue regeneration. Synthetic materials offer controllable biodegradability and customizable properties. Nano and hybrid materials provide enhanced mechanical and biochemical properties. These materials are used to create scaffolds that support axonal growth, reduce inflammation, and promote functional recovery. Fabrication techniques such as hydrogels, electrospinning, and 3D printing are used to create scaffolds with specific properties. Hydrogels can be injectable, allowing minimal surgical trauma, while electrospinning produces nano- to micron-scale fibers that support cell growth. 3D printing enables precise scaffold structures that match the SCI site. Biomaterial-based therapeutic strategies include managing inflammation, reducing oxidative stress, restoring the blood-spinal cord barrier, and reducing glial scarring. Anti-inflammatory treatments, antioxidant molecules, and nanozymes are used to modulate the immune environment and reduce secondary damage. Restoring the blood-spinal cord barrier is crucial for preventing immune cell infiltration and inflammation. Reducing glial scarring involves targeting astrocytes and CSPGs to promote axonal regeneration. These strategies aim to enhance neurorestoration by stimulating axonal regeneration and forming neuronal relay networks. The integration of biomaterials with growth factors, cells, and neurotrophic factors can promote functional recovery. Future research should focus on optimizing biomaterial properties, improving delivery systems, and understanding the complex interactions between biomaterials and the injured spinal cord microenvironment. This review provides a comprehensive overview of biomaterial-based approaches for SCI treatment and highlights the potential for further advancements in spinal cord regeneration.Biomaterial-based regenerative strategies for spinal cord injury (SCI) aim to repair the spinal cord by leveraging biomaterials, which can serve as scaffolds, drug delivery vehicles, or artificial bioactive niches. This review summarizes representative biomaterials, including natural, synthetic, nano, and hybrid materials, and their applications in SCI treatment. It also discusses advanced tissue engineering fabrication techniques and biomaterial-based therapeutic strategies to reduce secondary damage and promote repair. The review highlights clinical studies on functional bioscaffolds and provides insights for future research in spinal cord regeneration. Spinal cord injury leads to permanent neurological impairment due to complex pathological mechanisms and a unique post-injury microenvironment. Current treatments lack effectiveness in promoting SCI recovery. Tissue engineering has introduced new approaches using biomaterials to create favorable microenvironments for nerve regeneration. Biomaterials can be tailored to interact with the nervous system, providing spatial scaffolds, drug delivery, and artificial bioactive niches resembling the extracellular matrix. Natural materials such as collagen, fibrin, hyaluronic acid, chitosan, and alginate are used for their biocompatibility, biodegradability, and ability to support tissue regeneration. Synthetic materials offer controllable biodegradability and customizable properties. Nano and hybrid materials provide enhanced mechanical and biochemical properties. These materials are used to create scaffolds that support axonal growth, reduce inflammation, and promote functional recovery. Fabrication techniques such as hydrogels, electrospinning, and 3D printing are used to create scaffolds with specific properties. Hydrogels can be injectable, allowing minimal surgical trauma, while electrospinning produces nano- to micron-scale fibers that support cell growth. 3D printing enables precise scaffold structures that match the SCI site. Biomaterial-based therapeutic strategies include managing inflammation, reducing oxidative stress, restoring the blood-spinal cord barrier, and reducing glial scarring. Anti-inflammatory treatments, antioxidant molecules, and nanozymes are used to modulate the immune environment and reduce secondary damage. Restoring the blood-spinal cord barrier is crucial for preventing immune cell infiltration and inflammation. Reducing glial scarring involves targeting astrocytes and CSPGs to promote axonal regeneration. These strategies aim to enhance neurorestoration by stimulating axonal regeneration and forming neuronal relay networks. The integration of biomaterials with growth factors, cells, and neurotrophic factors can promote functional recovery. Future research should focus on optimizing biomaterial properties, improving delivery systems, and understanding the complex interactions between biomaterials and the injured spinal cord microenvironment. This review provides a comprehensive overview of biomaterial-based approaches for SCI treatment and highlights the potential for further advancements in spinal cord regeneration.