Lipid-based nanoplatforms appear to be one of the most promising groups of biomaterials for skin delivery. This is due to their favourable physicochemical, mechanical and safety properties. Gel-like matrices play an important role in medicine, pharmacy and cosmetology. The aim of the present study was to obtain a gel-like matrix based on freeze-dried nanostructured lipid carriers prepared with Softisan® 649 and Miglyol® 812 for the dermal delivery of genistein. The nanostructured lipid carriers were prepared and characterised by the hot ultrasound method. Genistein-loaded nanoparticles have a size around 235 nm, similar to empty nanoparticles (225 nm), and show storage stability up to 12 weeks at room temperature. Nanoencapsulation protected genistein from photodegradation and preserved its antioxidant activity. Biocompatibility assays showed that neither genistein-loaded nor empty lipid nanoparticles adversely affected HaCaT cell viability up to 100 μg mL−1 of genistein, while the IC50 of free genistein was 68.7 μg mL−1. The lipid nanoparticles were freeze-dried to obtain a gel-like matrix. The presence of genistein slightly reduces the swelling ability of the lipid-based gels, the gel-like matrix shows non-thixotropic behaviour and good resistance to deformation, which is not affected by the presence of genistein, indicating the stability of the nanoformulation. In vitro skin permeation assays show an increased skin deposition of genistein for the gel-like formulation compared to free isoflavone. The data obtained in the present study demonstrate the potential of the gel-like matrix to deliver genistein to the skin, suggesting a promising application as a supplement for sun protection and skin diseases associated with solar UV radiation.