OBJECTIVE To develop and characterize self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble drug, glibenclamide (GBD). METHODS Solubility of GBD was determined in various vehicles. Phase diagrams were constructed to identify efficient self-emulsification region using oils, surfactants, and cosurfactants in aqueous environment. Formulations were assessed for drug content, spectroscopic clarity, emulsification time, contact angle, zeta potential, particle size, and dissolution studies. On the basis of similarity and dissimilarity of particle size distribution, formulations were further characterized using principal component analysis and agglomerative hierarchy cluster analysis. RESULTS Among the formulations prepared and evaluated, optimized formulation showed mean particle size between 15.65 and 32.70 nm after 24 hour postdilution in various media. Dilution volume had no significant effect on particle size. Transmission electron microscopy of these formulations confirmed the spherical shape of globules with no signs of coalescence of globules and precipitation of drug. The relevance of difference in t(50%) and percent dissolution efficiency were evaluated statistically by two-way ANOVA. Infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction studies indicated compatibility between drug, oil, and surfactants. CONCLUSIONS The results of this study indicate that the self-nanoemulsifying drug delivery system of GBD, owing to nanosize, has potential to enhance its absorption and without interaction or incompatibility between the ingredients.