Oral drug delivery (ODD) is the most preferred and convenient route of drug administration due to high patient compliance, cost-effectiveness, least sterility constraints, flexibility in the design of dosage form and ease of production. However, the challenges faced in oral drug delivery include poor bioavailability of drug, which is determined by three vital factors, namely, dissolution, permeability, and solubility. In order to achieve effective drug absorption in vivo, various mathematical models have been designed to predict the dissolution and solubility rate of drug. Likewise, permeability is determined by cellular and noncellular models. In addition, behavior of the drug in gastrointestinal tract (GIT) is dependent on intrinsic factors of drug and physiological aspects, namely, pH, microbial colonization, and enzymes. Several pharmaceutical techniques have been contrived to stabilize and solubilize the active compounds in GIT, but it failed to attain a controlled and targeted release of the oral drug. This chapter overviews the strategy to override such drawbacks by ushering in various nanotechnology platforms like polymer based nanocarriers, lipid based nanocarriers, metal, and inorganic-based nanoparticles. © 2017 Elsevier Inc. All rights reserved.