INTRODUCTION: The present research aimed to address the drawbacks of oral conventional therapy for Parkinson's Disease (PD) by developing and testing a site-specific Imperatorin nanoemulgel that might improve upon it through improved brain-targeted delivery and therapeutic effectiveness. METHODS: A gel matrix containing carbopol 940 was used to produce imperatorin on a nanoemulsion scale, utilizing high-energy ultrasonication. After the nanoemulgel was made, its encapsulation efficiency, drug content, zeta potential, polydispersity index, and particle size were evaluated. In vivo efficacy was determined in an MPTP-induced PD rat model by means of behavioral testing (rotarod and open-field), biochemical assays (MDA, SOD, TNF-α). RESULTS: The optimized nanoemulgel had a particle size of 120 ± 10 nm, a zeta potential of -25.6 ± 2.1 mV, and an encapsulation efficiency of 92.7 ± 1.5%. It had a biphasic release of the drug with cumulative release of 95.6 ± 2.7% after 24 hours. In vitro assays validation assured increased antioxidant and anti-inflammatory activity compared to the control. In vivo, the nanoemulgel improved the motor function profoundly, decreased oxidative stress (MDA: 1.5 nmol/mg), and normalized antioxidant enzyme activity (SOD: 48.5 U/mg), and downregulated inflammation (TNF- α: 12.4 pg/mg) in PD rats. DISCUSSION: The imperatorin nanoemulgel performed well to enhance the delivery of the drug into the brain, suppressed PD-associated neurodegeneration, and enhanced behavioral and biochemical scores. CONCLUSION: This preparation holds a potential non-surgical management approach to PD control that justifies further clinical investigation.