A wide variety of peptide drugs are now produced on a commercial scale as a result of advances in the biotechnology field. Most of these therapeutic peptides are still administered by the parenteral route because of insufficient absorption from the gastrointestinal tract. Peptide drugs are usually indicated for chronic conditions, and the use of injections on a daily basis during long-term treatment has obvious drawbacks. In contrast to this inconvenient and potentially problematic method of drug administration, the oral route offers the advantages of self-administration with a high degree of patient acceptability and compliance. The main reasons for the low oral bioavailability of peptide drugs are pre-systemic enzymatic degradation and poor penetration of the intestinal mucosa. A considerable amount of research has focused on overcoming the challenges presented by these intestinal absorption barriers to provide effective oral delivery of peptide and protein drugs. Attempts to improve the oral bioavailability of peptide drugs have ranged from changing the physicochemical properties of peptide molecules to the inclusion of functional excipients in specially adapted drug delivery systems. However, the progress in developing an effective peptide delivery system has been hampered by factors such as the inherent toxicities of absorption-enhancing excipients, variation in absorption between individuals, and potentially high manufacturing costs. This review focuses on the intestinal barriers that compromise the systemic absorption of intact peptide and protein molecules and on the advanced technologies that have been developed to overcome the barriers to peptide drug absorption.