The majority of patients find that the oral route of drug administration is the most convenient, easy to follow, non- invasive, and physician-preferred method. However, oral biologic administration is not as beneficial as other routes because of mucosal permeability and various gastrointestinal barriers that limit the systemic absorption of complex macromolecules after ingestion. Because of their large molecular size, which results in extremely poor permeability across the intestinal mucosa, biologics are sensitive to the harsh environment of the gastrointestinal tract and thus play a significant role in the treatment of therapeutic interventions such as Chronic ailments, metabolic disease aging, and inflammatory disorders. Many drug delivery systems and pharmaceutical technologies, such as micelles, nano carriers, lipid-based carriers, and cyclodextrins, have been explored to enhance oral drug absorption. This article will first address the drug discovery, intensive research, and design that have enhanced the growth of biologics in recent decades and further accelerated the way we administer the medication in a clinical setting. physiological barriers to oral delivery of biologics and addresses various approaches to enhance the efficacy of oral delivery; furthermore, this conversation will encompass the diverse benefits and constraints of drug delivery systems as well as the general perception and promise of this emerging clinical area. Keywords: Absorption enhancers; biologics; drug delivery; Gastrointestinal barriers; insulin; microneedle pill; oral delivery.