The objective of this research work was to design, characterize and evaluate hesperidin loaded microemulsion to improve the solubility and dissolution rate. Pseudoternary phase diagrams were prepared to select the compo-nents of microemulsion and a mixture of sesame and orange oil, Tween (R) 80, and Solutol (R) HS15 were selected as oil phase, surfactant and cosurfactant, respectively. The microemulsion was extensively characterized for size, morphology, microstructure, pH, transmittance, thermal stability, storage stability and in vitro release studies. The in vitro drug release studies showed a faster release of hesperidin from the microemulsion in comparison to plain drug. Further, nasal ciliotoxicity studies performed on goat nasal mucosa demonstrated safety of the formulation for nose-to-brain administration. In vitro cell line studies in SH-SY5Y cells showed cytocompatibility and a dose-dependent uptake of the microemulsion globules. These findings suggests that hesperidin loaded microemulsion can be exploited as an effective therapeutic strategy for various neurodegenerative diseases.