Daidzein (DZ) has antioxidant, anti-inflammatory activities and also inhibits the growth of the cancer cells. The aim of this study is to formulate nanoemulsions (NEs) and nanoemulsion-based gels (NEGs) containing DZ, in order to evaluate their cytotoxic potential for topical application against melanoma. The NE formulations were prepared by using a high-pressure homogenization technique. Protasan ™ UP G 213 (1% w/w) was added to the NE formulation to prepare NEG formulations. Droplet size values were 151.12 ± 2.70 nm and 149.80 ± 3.52 nm for Blank-NE (B-NE) and DZ-NE, 191.48 ± 5.26 nm and 200.25 ± 11.09 nm for B-NEG and DZ-NEG, respectively. Positive zeta potential values for the NEG formulations were obtained in the presence of Protasan ™ UP G 213. All formulations had appropriate pH values for skin and also complied with zero-order release kinetics. The DZ release rates obtained for DZ-NE and DZ-NEG were 2.701 ± 0.265 and 1.325 ± 0.117 μg/cm2/hour, respectively. During the stability study, NE and NEG formulations had droplet sizes in the nano-range. All formulations maintained the cytotoxic effect of DZ against the melanoma cell line. NE and NEG formulations with a controlled release profile and nanometer droplet size may be useful for the topical use of DZ and the treatment of skin cancer.