<p>Spinal cord injuries (SCI) lead to severe disabilities and a significant burden on patients and healthcare systems. The enzyme chondroitinase ABC (ChABC) has demonstrated promise in promoting axonal regeneration by degrading inhibitory proteoglycans in glial scars, but its clinical use is limited due to thermal instability and rapid inactivation at body temperature. This review extensively discusses various stabilization strategies of ChABC including protein engineering, immobilization, and use of stabilizing chemicals. Protein engineering techniques like site-specific mutagenesis aim to enhance stability by modifying amino acids, while immobilization methods utilize appropriate carriers such as nanoparticles or hydrogels to protect the enzyme from degradation. Encapsulation in protective structures maintains activity over extended periods and chemical stabilizers such as polyols preserve enzyme functionality at physiological temperatures. Each method has unique benefits and challenges, but collectively, they offer significant potential for improving ChABC stability in SCI treatment. Enhanced stability of ChABC prolongs the efficacy period, which in turn leads to more effective and less invasive therapies; therefore, better neuronal regeneration and functional recovery of SCI can be acquired.</p>