Exosomes, naturally occurring nanovesicles, have been explored as drug delivery vehicles for Parkinson's disease (PD) therapy. This study developed a new exosomal-based delivery system for catalase, a potent antioxidant, to treat PD. Catalase was loaded into exosomes using various methods, including incubation at room temperature, saponin permeabilization, freeze-thaw cycles, sonication, and extrusion. The resulting exoCAT formulations had sizes between 100-200 nm and showed high loading efficiency, sustained release, and resistance to protease degradation. ExoCAT was efficiently taken up by neuronal cells in vitro and detected in PD mouse brains after intranasal administration. ExoCAT provided significant neuroprotective effects in both in vitro and in vivo PD models. Exosomes, secreted by immune cells, can bypass the mononuclear phagocyte system and deliver drugs to target cells, making them promising for CNS drug delivery. Exosomes can cross biological barriers and have been used to deliver drugs, siRNA, and therapeutic agents. Exosomes can also exert biological activity based on their origin. Exosomes derived from macrophages can release catalase and facilitate drug transfer to target cells. ExoCAT formulations showed improved catalase activity, prolonged circulation time, and reduced immunogenicity. ExoCAT was effective in reducing oxidative stress and increasing neuronal survival in PD models. Exosomes may be a versatile strategy for treating inflammatory and neurodegenerative disorders. The study evaluated the manufacturing, characterization, and therapeutic efficacy of exoCAT. ExoCAT formulations were characterized by DLS, AFM, NTA, and hyperspectral microscopy. ExoCAT showed high catalase loading efficiency, sustained release, and resistance to protease degradation. ExoCAT was efficiently taken up by PC12 cells and showed neuroprotective effects against oxidative stress. ExoCAT was transported into the brain of PD mice and showed neuroprotective effects. ExoCAT reduced microglial activation, astrocytosis, and neuronal loss in PD models. ExoCAT also improved motor function in apomorphine tests. ExoCAT showed no toxic effects on healthy mice. Exosomes may be a promising delivery system for PD therapy due to their ability to cross the blood-brain barrier, avoid immune detection, and deliver drugs to target cells. This study demonstrates the potential of exosome-based catalase formulations for PD treatment.Exosomes, naturally occurring nanovesicles, have been explored as drug delivery vehicles for Parkinson's disease (PD) therapy. This study developed a new exosomal-based delivery system for catalase, a potent antioxidant, to treat PD. Catalase was loaded into exosomes using various methods, including incubation at room temperature, saponin permeabilization, freeze-thaw cycles, sonication, and extrusion. The resulting exoCAT formulations had sizes between 100-200 nm and showed high loading efficiency, sustained release, and resistance to protease degradation. ExoCAT was efficiently taken up by neuronal cells in vitro and detected in PD mouse brains after intranasal administration. ExoCAT provided significant neuroprotective effects in both in vitro and in vivo PD models. Exosomes, secreted by immune cells, can bypass the mononuclear phagocyte system and deliver drugs to target cells, making them promising for CNS drug delivery. Exosomes can cross biological barriers and have been used to deliver drugs, siRNA, and therapeutic agents. Exosomes can also exert biological activity based on their origin. Exosomes derived from macrophages can release catalase and facilitate drug transfer to target cells. ExoCAT formulations showed improved catalase activity, prolonged circulation time, and reduced immunogenicity. ExoCAT was effective in reducing oxidative stress and increasing neuronal survival in PD models. Exosomes may be a versatile strategy for treating inflammatory and neurodegenerative disorders. The study evaluated the manufacturing, characterization, and therapeutic efficacy of exoCAT. ExoCAT formulations were characterized by DLS, AFM, NTA, and hyperspectral microscopy. ExoCAT showed high catalase loading efficiency, sustained release, and resistance to protease degradation. ExoCAT was efficiently taken up by PC12 cells and showed neuroprotective effects against oxidative stress. ExoCAT was transported into the brain of PD mice and showed neuroprotective effects. ExoCAT reduced microglial activation, astrocytosis, and neuronal loss in PD models. ExoCAT also improved motor function in apomorphine tests. ExoCAT showed no toxic effects on healthy mice. Exosomes may be a promising delivery system for PD therapy due to their ability to cross the blood-brain barrier, avoid immune detection, and deliver drugs to target cells. This study demonstrates the potential of exosome-based catalase formulations for PD treatment.