The formation of a biomolecular corona on exogenous particles in plasma is well studied and is known to dictate the biodistribution and cellular interactions of nanomedicine formulations. In contrast, while the oral route is the most favorable administration method for pharmaceuticals, little is known about the formation and composition of the corona formed by biomolecules on particles within the gastrointestinal tract. This work reviews the current literature understanding of (1) the formation of drug particles after oral administration, (2) the formation of a biomolecular corona within the gastrointestinal tract ("the gastrointestinal corona"), and (3) the possible implications of the formation of a gastrointestinal corona on the interactions of drug particles with their biological environment. In doing so, this work aims to establish the significance of the formation of a gastrointestinal corona in oral drug delivery to ultimately arrive at new avenues to control the behavior of orally administered pharmaceuticals.