Background: The oral route is the most frequently used and the most convenient route of drug administration since it has several advantages, such as ease of use, patient compliance, and better costeffectiveness. However, physicochemical and biopharmaceutical limitations of various active pharmaceutical ingredients (API) hinder suitability for this route, including degradation in the gastrointestinal tract, low intestinal permeability, and low bioavailability. To overcome these problems, while maintaining therapeutic efficacy, polymeric nanoparticles have attracted considerable attention for their ability to increase drug solubility, promote the controlled release, and improve stability. In addition, the functionalization of nanocarriers can increase uptake and accumulation at the target site of action, and intestinal absorption, making it possible to obtain more viable, safe and efficient treatments for oral administration. Objective: This systematic review aimed to seek recent advances in the literature on the use of polymeric nanoparticles functionalization to increase intestinal permeability of APIs that are intended for oral administration. Method: Two bibliographic databases were consulted (PubMed and ScienceDirect). The selected publications and the writing of this systematic review were based on the guidelines mentioned in the PRISMA statement. Results: Out of a total of 3036 studies, 22 studies were included in this article based on our eligibility criteria. The results were consistent for the application of nanoparticle functionalization to increase intestinal permeability. Conclusion: The functionalized polymeric nanoparticles can be considered as carrier systems that improve the intestinal permeability and bioavailability of APIs, with the potential to result, in the future, in the development of oral medicines.