Neurotransplantation and regenerative therapies hold immense potential for treating neurodegenerative diseases by replenishing lost neuronal populations, modulating disease progression, and enhancing endogenous repair mechanisms. This chapter provides a comprehensive overview of the importance of preclinical models in advancing neurotransplantation research, highlighting both their advantages and inherent limitations. A detailed examination of various transplantation strategies is presented, including the use of embryonic, induced pluripotent, neural and mesenchymal stem cells, and olfactory ensheathing cells, along with their respective differentiation capacities, integration potential, and therapeutic effects. The chapter further explores cellular mechanisms underlying neurotransplantation, such as direct cell replacement, neurotrophic factor secretion, Immune modulation, and synaptic integration, all of which contribute to functional recovery. A critical assessment of experimental transplantation efforts in Preclinical models of Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, amyotrophic lateral sclerosis, spinal cord injury, and optic nerve degeneration is included, showcasing both successes and persistent challenges. Key considerations for successful transplantation are discussed, including optimizing differentiation protocols, mitigating immune rejection, and improving long-term cell survival and functional integration. Future research directions emphasize the need for personalized therapies, combination approaches with pharmacological and rehabilitative interventions, and the incorporation of biomaterial scaffolds to enhance transplantation outcomes. By addressing these challenges, the field of neuroregenerative medicine moves closer to effective clinical applications, offering renewed hope for patients suffering from debilitating neurodegenerative conditions.