Lipophilic compounds constitute a majority of therapeutics in the pipeline of drug discovery. Despite possessing enhanced efficacy and permeability, some of these drugs suffer poor solubility necessitating the need of a suitable drug delivery system. Nanoemulsion is a drug delivery system that provides enhanced solubility for poorly soluble drugs in an attempt to improve the oral bioavailability. The purpose of this study is to develop a nanoemulsion system using ibuprofen as a model drug in order to investigate the potential of this colloidal system to enhance the absorption of poorly water-soluble drugs. Ibuprofen loaded-nanoemulsion with different drug concentrations (1.5, 3 and 6% w/w) were formulated from olive oil, sucrose ester L-1695 and glycerol using D-phase emulsification technique. A pseudoternary phase diagram was utilised to identify the optimal excipient composition to formulate the nanoemulsion system. In vitro diffusion chamber studies using rodent intestinal linings highlighted improved absorption profile when ibuprofen was delivered as nanoemulsion in comparison to microemulsions and drug-in-oil systems. This was further corroborated by in vivo studies using rat model that highlighted a two-fold increase in ibuprofen absorption when the drug was administered as a nanoemulsion relative to drug-in-oil system. On the other hand, when ibuprofen was administered as microemulsions, only a 1.5-fold increase in absorption was observed relative to drug-in-oil system. Thus, this study highlights the potential of using nanoemulsion as a drug delivery system to enhance the oral bioavailability of hydrophobic drugs.