The goal of the current study was to investigate the therapeutic effects of exosomes derived from mesenchymal stem cells (MSCs-Exo) and copper sulfide nanoparticles (CuSNPs) as biomaterials in order to understand the mechanisms that contribute to overcoming cadmium (Cad) induced neurological disorders in rats. Animals were divided into five groups (n = 10): group 1 was served as a negative control and receive vehicle saline (Con), group 2 Positive control groups were received Cad as cadmium chloride at a dose of 20 mg/kg/day for six weeks (Cad group), group 3 was received Cad plus MSCs-Exo as a single dose of 100 μLi. v. (Cad + MSCs-Exo), group 4 was received Cad plus CuSNPs at a dose of 6.5 mg/kg orally (Cad + CuSNPs), group 5 was received Cad + MSCs-Exo + CuSNPs for six weeks. However, the activities of each acetylcholine (Ach), acetylcholinesterase (AchE), total antioxidant status (TAC) were measured. Also, the levels of ROS, nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), Brain brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were evaluated. Beneficial effects on the behavior of animals were observed after treatment with MSCs-Exo and CuSNPs. Furthermore, the administration of MSCs-Exo and CuSNPs have been improve the TAC, BDNF and NGF via ameliorating the oxidative stress and inflammatory markers. Moreover, Histopathological studies had shown that great development in the brain of Cad rats treated with MSCs-Exo and CuSNPs. In conclusion, this study offers an overview of innovative stem cell therapy techniques and how to integrate them with nanotechnology to boost therapeutic performance.