Hydrochlorothiazide (HCT) is a widely used diuretic in combination with cardiovascular drugs for the treatment of hypertension. Low solubility and low permeability of HCT cause possible deviation in its oral bioavailability. Therefore, the objective of the current work was to develop optimized self nano emulsifying drug delivery system (SNEDDS) to enhance the solubility and permeability of HCT and, as a consequence, its bioavailability. Solubility of hydrochlorothiazide was determined in various oils, surfactants and co-surfactants. Based on pseudoternary phase diagram studies, various HCT SNEDDS were formulated. Prepared SNEDDS were evaluated by in vitro dissolution studies, viscosity determination, globule size, zeta potential analysis, emulsification time studies and in vivo pharmacodynamic profiling. SNEDDS exhibited a remarkable increase in rate of dissolution of HCT in comparison with plain drug and marketed formulation. Average droplet size of optimized formulation was found to be 42.84 nm. In vivo pharmacodynamic evaluation in Wistar rats showed considerable increase in pharmacological effect of HCT by SNEDDS formulation as compared with plain HCT. Current study demonstrated that SNEDDS can be utilized as possible alternative for enhanced efficacy of HCT.