Nanoemulsion formulations for the transdermal delivery of glipizide, a second-generation sulfonylurea designed to manage type 2 diabetes. Glipizide was designed to have a high level of solubility, bioavailability, and controlled release using nanoemulsions that consisted of oil, surfactants and co-surfactants to promote the release of the drug. Various formulations (F1-F6) were prepared based on the oils such as ACC 200 E6, surfactants such as Cr RH40 and T-80, and co-surfactants such as PEG 400. The formulations were subjected to solubility, phase diagram development, and testing thermodynamic stability in order to attain optimum nanoemulsification and stability. The findings presented that the formulations had very high physical stability and uniform drug content (99.36-100.56%), and clear optical appearance and no separation of the phases. The size of the droplets remained constant and this guaranteed effective absorption. The presence of higher stability was demonstrated by zeta potential analysis; formulations contained positive values of zeta potential (15.9024.80 mV), which is essential during skin interaction. In vitro release assays showed different release patterns with the percentage of drug release ranging 45.78-59.33. The formulations were characterized by the controlled release, and promising opportunities in terms of glipizide as a therapeutic agent in transdermal delivery provided a sustained effect