The aim of the present study was to develop water-in-oil-in-water (w/o/w) type Multiple Emulsion of Lisinopril dihydrate for enhancing its oral bioavailability via enhanced permeation. For primary emulsification, corn oil was used as the oil phase, Span 83 as the lipophilic surfactant and Xanthan gum was used as the viscosity enhancer. Primary emulsion was re-emulsified with aqueous phase containing Tween 20 as hydrophilic surfactant. Preliminary screening was performed using a 12-run, 8-factor, 2-level Plackett–Burman design followed by Box Behnken Design for optimization. MEs were characterized and evaluated for macroscopic and microscopic properties, globule size, entrapment efficiency, rheological properties, in vitro and ex vivo drug release and stability studies. In vitro drug diffusion study was done through dialysis bag and ex vivo permeability studies were performed in Franz diffusion cell using rat intestine. The optimized w/o/w ME showed globule size and entrapment efficiency of 15.65 + 1.967 μm and 87.35 + 3.79 % respectively. Drug flux was found to be 119.3 μg/cm2/h for drug loaded w/o/w ME and 105.1μg/cm2/h for plain drug solution. The overall results of the studies showed the potential of the w/o/w ME as promising drug delivery system for Lisinopril dihydrate.