Abstract. The objective of the current study was to formulate oxybenzone into nanostructured lipid carriers (NLCs) to enhance its sunscreening efficacy and safety. NLCs of oxybenzone were prepared by the solvent diffusion method. A complete 2 3 factorial design was used for the evaluation of the prepared oxybenzone NLCs. The study design involves the investigation of the effect of three independent variables namely liquid lipid type (Miglyol 812 and oleic acid), liquid lipid concentration (15% and 30%), and oxybenzone concentration (5% and 10% with respect to total lipids) on the particle size (p.s.) , the entrapment efficiency (EE%) and the in vitro drug release after 8 h. The prepared NLCs were spherical in overall shape and were below 0.8 μm. Miglyol 812 and 30% liquid lipid were found to significantly decrease the p.s. and increase the EE% when compared to oleic acid and 15% liquid lipid. Increasing oxybenzone concentration increased significantly the p.s. but did not affect the EE%. NLCs prepared using Miglyol 812, 15% liquid lipid, and 10% oxybenzone showed slower drug release when compared to those prepared using oleic acid, 30% liquid lipid, and 5% oxybenzone, respectively. The candidate oxybenzone-loaded NLC dispersion was then formulated into gel. The incorporation of oxybenzone into NLCs greatly increased the in vitro sun protection factor and erythemal UVA protection factor of oxybenzone more than six-and eightfold, respectively, while providing the advantage of overcoming side effects of free oxybenzone as evidenced by very low irritation potential.