While it is the most convenient and less invasive route of delivery, oral administration is difficult and rarely used for biologics. Indeed, these macromolecules are sensitive to the harsh environment of the gastrointestinal tract, and their large size considerably limits their passive permeability across the intestinal epithelium (>500 Da). To address these challenges, the research conducted within my thesis aimed at using the advantageous features of 7 kDa affinity proteins, the Nanofitins, to cross actively the intestinal mucosa by targeting the leptin receptor. During this PhD project, Nanofitins with a specific affinity to the target were thus generated and their ability to cross the intestinal barrier has been investigated using an ex vivo porcine intestinal model. We obtained promising results demonstrating a specific receptor-mediated transport of Nanofitins. These data support their use for the oral delivery of targeted therapies and their further evaluation in an in vivo model.