The topical delivery of plant-derived natural products is often limited by their high lipophilicity, poor aqueous solubility, and formulation instability. This thesis aimed to develop aqueous nanocarrier formulations and investigate their ability to enhance the cutaneous delivery of highly lipophilic natural products from both single compounds and complex plant mixtures. Cutaneous biodistribution was investigated using the cutaneous biodistribution method (CBM), combining cryosectioning with UHPLC-MS/MS to enable depth-resolved monitoring of single and multiple lipophilic compounds. Among the nanocarrier systems evaluated, nanoemulsions outperformed micelles and microemulsions, improving delivery to the viable epidermis and dermis, with evidence of preferential deposition in hair follicles. Importantly, this work also investigated biodistribution over extended periods using a viable ex vivo skin culture model to better represent real-life topical application, revealing progressive accumulation of bioactive compounds in the epidermis and upper dermis while maintaining tissue integrity. These findings demonstrate the potential of nanoemulsion-based formulations and advanced biodistribution analysis for improving the topical delivery of lipophilic natural products.