The present work is focused on the preparation of an optimal model of poly-ε-caprolactone nanoparticles as potential carriers for nasal administration of idebenone. A solvent/evaporation technique was used for nanoparticle preparation. Poly-ε-caprolactone with different molecular weights (14,000 and 80,000 g/mol) was used. Polysorbate 20 and Poloxamer 407, alone and in combination, were used as emulsifiers at different concentrations to obtain a stable formulation. The nanoparticles were characterized using dynamic light scattering, SEM, TEM, and FTIR. The resulting structures were spherical in shape and their size distribution depended on the type of emulsifier. The average particle size ranged from 188 to 628 nm. The effect of molecular weight and type of emulsifier was established. Optimal models of appropriate size for nasal administration were selected for inclusion of idebenone. Three models of idebenone-loaded nanoparticles were developed and the effect of molecular weight on the encapsulation efficiency was investigated. Increased encapsulation efficiency was found when poly-ε-caprolactone with lower molecular weight was used. The molecular weight also affected the drug release from the nanostructures. Dissolution study data were fitted into various kinetic models and the Korsmeyer–Peppas model was found to be indicative of the release mechanism of idebenone.