This research aimed at formulating transethosomal film-forming gel (TG) of domperidone- an antiemetic and anti-sickness drug. The prepared transethosomes (TE) were optimized and the vesicle size, PDI and %EE of the optimized TE was 15.1nm, 0.387 and 73.82 respectively where the %error was <±5% of the predicted value. The prepared formulation was further characterized for zeta potential, optical microscopy and transmission electron microscopy. The nano-vesicular systems were then incorporated into a film forming gel and evaluated for in vitro drug release and ex vivo skin permeation studies. The amount of drug released after 8 h for was found to be 49.67% for conventional gel (CG) and 36.079% for transethosomal gel (TG). TG followed first-order release kinetics and Higuchi model as the release mechanism. The steady-state flux of drug from TG after 8 h was found to be 2.51 times that of the CG. A skin irritation study was conducted using Wistar rats and the formulation showed no irritation to the skin. Stability testing was done and the formulation remained stable over the time period. It was concluded that domperidone-loaded TG can be a promising alternative for oral drug formulations due to the sustained release of the drug.