A new positively charged nanoemulsion using quaternized chitosan (QCS) as a protective layer was developed to improve the stability and bioactivity of lipophilic active components. The anti-inflammatory Plai extract was chosen as both an active ingredient and an oil phase of the system. Compared with chitosan-coated nanoemulsion (NE2-CS) and uncoated nanoemulsion (NE1), the QCS coating could improve the stability of the Plai extract during 28 days. The particle size of NE1 increased from 141 nm to 202 nm after coating with QCS, whereas zeta potential changed from -22.03 mV for NE1 to 20.23 mV for NE2-QCS, confirming the presence of QCS. A clear improvement in anti-inflammatory, anti-cancer, and transdermal properties of Plai extract was verified for NE2-QCS, which could be due to the NEs' fineness and the permanent positive charge of the protective layer. Therefore, we suggested that QCS-coated NEs can be used as an effective transdermal delivery system for lipophilic active components.