Citric acid and glycerol play an important role in the food and drug industries. In this work, we present for the first time a facile and gram scale method for the preparation of polyglycerol-citric acid nanoparticles (PGCN) in the presence of silica gel blue as both catalyst and water removal agent. PGCN are highly biocompatible without significant toxicity up to 1 mg/ml. They are able to load small guest molecules and transfer them through the cell membrane, efficiently. Taking advantage of their straightforward synthesis and high biocompatibility as well as their ability to load and transfer small guest molecules, PGCN could be used for a variety of future biomedical applications.