The article reviews the current and promising oral delivery methods for protein- and peptide-based drugs (PPDs). Despite the preference for oral administration due to improved patient compliance, PPs are typically administered parenterally due to their instability in the gastrointestinal (GI) tract and limited permeability across physiological barriers. The review discusses various strategies to enhance the oral absorption of PPs, including the use of nanoparticles, transport channels, permeation enhancers, chemical modifications, hydrogels, microneedles, microemulsions, proteolytic enzyme inhibitors, and cell-penetrating peptides. These methods aim to overcome the challenges posed by the harsh conditions in the GI tract, such as pH variations, digestive enzymes, and mucus layers. The article also highlights the development of oral PPs, including cyclosporine, insulin, semaglutide, octreotide, and desmopressin, which have been approved for medical use or are under ongoing research. The potential of these methods and the physiological barriers they aim to overcome are illustrated through graphical representations and a summary table.The article reviews the current and promising oral delivery methods for protein- and peptide-based drugs (PPDs). Despite the preference for oral administration due to improved patient compliance, PPs are typically administered parenterally due to their instability in the gastrointestinal (GI) tract and limited permeability across physiological barriers. The review discusses various strategies to enhance the oral absorption of PPs, including the use of nanoparticles, transport channels, permeation enhancers, chemical modifications, hydrogels, microneedles, microemulsions, proteolytic enzyme inhibitors, and cell-penetrating peptides. These methods aim to overcome the challenges posed by the harsh conditions in the GI tract, such as pH variations, digestive enzymes, and mucus layers. The article also highlights the development of oral PPs, including cyclosporine, insulin, semaglutide, octreotide, and desmopressin, which have been approved for medical use or are under ongoing research. The potential of these methods and the physiological barriers they aim to overcome are illustrated through graphical representations and a summary table.