Background Oral administration is the preferred route for drug delivery due to convenience and patient compliance, yet its efficacy is hampered by low solubility and enzymatic degradation. Nanoparticulate drug delivery systems (NDDS) have emerged as a strategic solution to overcome these gastrointestinal (GI) barriers.Objective To systematically evaluate the impact of nanoparticle-based drug delivery systems on enhancing oral bioavailability (BA).Methods A systematic literature search was conducted using databases such as PubMed and Google Scholar following PRISMA guidelines. Studies comparing NDDS to conventional formulations using pharmacokinetic parameters (AUC, Cmax) were prioritized.Results The review identifies that nanoparticles (NPs) consistently improve oral BA, with improvements ranging from 2-fold to over 40-fold depending on the drug and carrier type.Conclusion NDDS represent a robust technology for improving the BA of poorly soluble drugs, though clinical translation remains the primary challenge