Nanostructured lipid carriers (NLC) are interesting delivery systems for enhancing the penetration of an active substance through the skin after topical administration. In the present study, lycopene was loaded into NLC, composed of Eumulgin® SG, orange wax and rice bran oil, using high pressure homogenization (HPH). Photon correlation spectroscopy analysis showed that the lycopene-loaded NLC had a size of 150–160 nm with a relatively small size distribution (PdI < 0.15). The entrapment efficiency of lycopene was found to be 100 ± 0% for all formulations. An in vitro release study of lycopene showed a biphasic release profile: a relatively fast release during the first 6 h followed by a sustained release during the next 18 h. An in vitro occlusion test showed that the occlusive properties of NLC increased with increasing lycopene loading. A free radical scavenging activity test of the NLC loaded with 50 mg% lycopene showed a Trolox equivalent antioxidant capacity value of 36.6 ± 0.4 μM Trolox/mg NLC which is higher than that of the NLC base (26.6 ± 0.1 μM Trolox/mg NLC). The concentration of 50% antioxidant activity (IC50) of the lycopene-loaded NLC was 14.1 ± 0.6 mg/mL, and lower than that of the formulation without lycopene (17.7 ± 0.4 mg/mL). The particle size, size distribution, and zeta potential of lycopene-loaded NLC stored at different temperatures of 4, 30, 40 °C for 120 days did not change in time, demonstrating an excellent colloidal stability of the systems. Chemical stability data indicated that the utilization of NLC increased the stability of lycopene and it was found that the degradation of lycopene was retarded when stored at low temperatures. In conclusion, NLC are attractive systems for the cutaneous delivery of lycopene.