Objective: The present study was aimed to develop a novel o/w self-emulsifying drug delivery system (SEDDS)with novel synthetic oils, a variety of natural oils and surfactants/co surfactants to enhance the solubility and dissolution rate of poorly water soluble drug, glibenclamide thereby to improve its relative bioavailability. The novelty in this proposed research work is the simple process of production and easy to scale up with minimum infrastructure. Methods: The design of an optimal SEDDS is performed by preformulation solubility and ternary phase-diagram studies. The prepared self - emulsifying formulations were performed for in vitro evaluation studies of droplet size, polydispersity index, drug loading, zeta potential, optical clarity, turbidity, cloud point, viscosity determination, self-emulsification time assessment, in vitro drug release and in vitro diffusion studies. Results: The results showed that Peceol as oil, Labrasol as surfactant and Transcutol HP as cosurfactant prepared stable emulsions has a refractive index as same that of water clearly indicated that the microemulsions was highly transparent. The percentage drug release for optimal formulation of glibenclamide SEDDS after 30 minutes was found to be 99.7 % when compared to API (active pharmaceutical ingredient) and marketed tablet. Conclusion: This study demonstrated that in vitro drug release and in vitro diffusion study were dependent on critical parameters such as particle size and drug loading in SEDDS formulations.