The objective of this study was to prepare a stable self-nanoemulsifying formulation of exendin-4, which is an antidiabetic peptide. As exendin-4 is commercially available only in subcutaneous form, several attempts have been made to discover an effective oral formulation. Self-nanoemulsifying drug delivery systems are known to be suitable carriers for the oral administration of peptide drugs. Various ratios of oil, surfactant, and co-surfactant mixtures were used to determine the area in the pseudoternary phase diagram for clear nanoemulsion. The Design of Experiment approach was used for the optimization of the formulation. Blank self-nanoemulsifying formulations containing ethyl oleate as oil phase, Cremophor EL(R), and Labrasol(R) as surfactant, absolute ethanol, and propylene glycol as co-solvent in various proportions were approximately 18-50 nm, 0.08-0.204 and - 3 to - 23 mV in droplet size, polydispersity index, and zeta potential, respectively. When all formulations were compared by statistical analysis, five of them with smaller droplet sizes were selected for further studies. The physical stability test was performed for 1 month at 5 degrees C +/- 3 degrees C and 25 degrees C +/- 2 degrees C/60% RH +/- 5% RH storage conditions. As a result of the characterization and physical stability test results, ethyl oleate: Cremophor EL(R):absolute ethanol (30:52.5:17.5) formulation and four formulations containing ethyl oleate: Cremophor EL(R):Labrasol(R):propylene glycol:absolute ethanol at varying concentrations were considered for peptide encapsulation efficiency. Formulation having the highest encapsulation efficiency of exendin-4 containing ethyl oleate: Cremophor EL(R):Labrasol(R):propylene glycole:absolute ethanol (15:42.5:21.25:15.94:5.31) was selected for in vitro Caco-2 intestinal permeability study. The permeabiliy coefficient was increased by 1.5-folds by exendin-4-loaded self-nanoemulsifying formulation as compared to the exendin-4 solution. It can be concluded that intestinal permeability has been improved by self-nanoemulsifying formulation.