BACKGROUND: Oral drug delivery is widespread owing to its non-invasive nature which complements high patient compliance. However, the drug administration via oral route is quite challenging due to the presence of the biochemical barriers which hinders the uptake as well as access to blood stream. Apart from that, stability, poor solubility and bioavailability of administered drug via the gastrointestinal (GI) tract are also exigent. Till now various oral formulations were developed which releases the drug in a timely manner but lacks appropriate therapeutic concentration. OBJECTIVE: Recently nanoparticles based drug delivery system has emerged as prominent strategy for optimizing the oral drug delivery and maximizing the treatment efficiency. Besides, different strategic polymeric nanoparticles are engineered for interaction both at extracellular and intracellular levels with gastrointestinal mucosa. METHODS: The review article focuses on the polymeric and lipid based various nanocarriers that have been widely studied for the enhanced oral drug delivery of different therapeutic molecules and addresses recent progress of biocompatible and biodegradable polymeric nanoparticles approach for its improvement. CONCLUSION: The progress of numerous oral nanoparticulate drug delivery vehicles will be immensely helpful to improve therapeutic efficacy with reduced adverse side effects. Unlike other forms of administration, it will have better patient compliance and soothing effect. The oral drug delivery will certainly play a pivotal role soon in expanding the clinical repertoire and applications.