Marine-derived natural bioactives have slowly emerged as a potential class of therapeutics in the treatment of complex central nervous system disorders, specifically brain and spinal cord injuries. In this systematic review, key compounds from a multitude of marine organisms will be explored, highlighting their effects as possible therapeutics due to their neuroprotective, anti-inflammatory, regenerative, and oxidative properties. These compounds are shown to modulate crucial pathological mechanisms (i.e., neuroinflammation, blood-brain barrier disruption, etc.), stimulating neurogenesis and axonal regeneration. Many therapeutics, such as ziconotide, bryostatin-1, manzamines, and fucoidan, have exhibited significant efficacy in preclinical and clinical models through targeted modulation of calcium channels, protein kinase C, and inflammatory cytokine pathways. Additionally, preventive agents like astaxanthin, omega-3 fatty acids, neuroprotectin D1, and squalamine promote significant health benefits, combating against neurodegeneration and stroke, through antioxidant and neurovascular stabilizing effects. Diagnostic applications, including labeled peptides and marine toxins, provide novel avenues for imaging and injury monitoring. Overall, this review highlights ongoing clinical trials and prospects in personalized neurology and integrative CNS care, underscoring the ocean’s untapped pharmacological potential. Marine bioactives represent a vital frontier in both therapeutic intervention and preventative strategy for CNS trauma and degeneration.