Transdermal patches have become a widely used approach for painless delivery of drugs. One major current limitation of these systems remains the restricted skin permeation of proteins and peptides as exemplified by insulin, necessitating different considerations for their successful transdermal delivery. We present a novel patch design based on the integration of nano-engineered heating elements on polyimide substrates for electrothermal transdermal therapy. The results reveal that tuning of the electrical resistivity of an array of gold nanoholes, patterned on polyimide, facilitates a fast-responding electrothermal skin patch, while post-coating with reduced graphene oxide offers capabilities for drug encapsulation, like insulin. Application of insulin-loaded patches to the skin of mice resulted in blood glucose regulation within minutes. While demonstrated for insulin, the skin patches might be well adapted to other low and high molecular weight therapeutic drugs, enabling on-demand electrothermal transdermal delivery.