Administration of drugs through the oral route is considered the simplest and most convenient way to offer greater patient compliance than other routes. Most active drugs discovered in the past and those being discovered in recent times are inadequate because of their inherent limitations in physicochemical properties such as low solubility and permeability, resulting in poor bioavailability, especially after oral administration in the form of tablet or capsule. Pharmaceutical nanoemulsion is the most promising, safer, and multimodal technique for delivering poorly soluble drugs and gaining more attention due to its characteristics such as higher solubilisation capacity, smaller size, surface charge, and site-specific drug targeting. This chapter focuses on the biological fate of nanoemulsion after oral administration and a few case studies related to the oral application of nanoemulsion in delivering poorly soluble drugs. In addition, the anatomy and physiology of the GI tract, components of nanoemulsion, and methods of preparation are addressed.