Oral administration of biologics such as peptides, proteins, vaccines, and nucleic acids is one of the most significant challenges because of enzymatic breakdown, acidic gastric environment, and low absorption in the intestines. Polymeric nanoparticle has become a potential solution to surmount these obstacles, as it provides protection of biologics, controlled release as well as increased mucosal uptake. This review will present a pharmaceutics-oriented overview of recent developments in polymeric nanoparticle-based oral delivery systems with particular emphasis on preclinical animal studies. The significant advances in natural and synthetic polymers, surface modification techniques including mucoadhesion, conjugation of ligands and pH- sensitive coatings and the applications in different classes of biologics are also critically examined. The animal studies show enhanced oral bioavailability, prolonged therapeutic effect and improved immune response, showing the potential of the systems as less invasive methods of administration compared to the conventional administration. Although some of these advances have been made, issues of formulation complexity, reproducibility, large-scale production and long-term safety have yet to be resolved. This review highlights the existing gaps and suggests future research to enable translation of polymeric nanoparticles in oral biologic delivery into clinical practice.