20(S)-protopanaxadiol (20S-PPD) is a fully deglycosylated ginsenoside metabolite and has potent dermal anti-aging activity. However, due to its low aqueous solubility and large molecular size, a suitable formulation strategy is required to improve its solubility and skin permeability, thereby enhancing its skin deposition. Thus, we optimized microemulsion (ME)-based hydrogel (MEH) formulations for the topical delivery of 20S-PPD.