Two most promising treatment strategies for multiple sclerosis (MS) are the administration of mesenchymal stem cells (MSCs) and targeted delivery of cerebrolysin. Comparing these treatment plans as a source of neurotrophic factors (NTFs) can inform future MS treatment guidelines. This study was carried out on the experimental autoimmune encephalomyelitis as an animal model of MS through NTFs-loaded TGN-modified chitosan nanoparticles ([email protected]) and MSCs administration. The clinical scores considerations and evaluation of biological samples were shown significant improvement in locomotion activity accompanied by a decrease in lymphocyte infiltration on spinal cord tissues in the [email protected] received group. These alterations may be modulated through GATA3/FOXP3 and targeting Th1/2 cells pathways. Our data shows that the targeted drug delivery strategies and high accessibility to the central nervous system may be a suitable option in the management of MS compared to cell therapy and pure NTFs administration.