Protein drugs represent a significant part of the new pharmaceuticals coming on the market every year and are now widely spread in therapy to treat or relief symptomatology related to many metabolic and oncologic diseases. The delivery of therapeutic proteins is still a major drawback against their maximum pharmacodynamic due to their physicochemical properties, poor stability, permeability and biodistribution. Despite the fact that the parenteral route remains the primary route of protein administration, research continues on non-parenteral delivery routes. However, the high molecular weight of proteins, combined with their hydrophilic and charged nature, renders transport through membranes very difficult. In this regard, the biopolymer chitosan exhibits several favorable biological properties, such as biocompatibility, biodegradability, low-toxicity and mucoadhesiveness, which made it a promising candidate for the formulation of protein drugs. The success of a protein formulation depends not only on the stability of the delivery system but also on their ability to maintain the native structure and activity of the protein during preparation and the delivery, as well as during longterm storage of the formulation. Chitosan-based delivery systems have been proposed as valid approaches to provide such protective conditions. The development of novel protein delivery systems based on chitosan is a rising subject irrespective of the intended route of administration. In this review, the different approaches recently exploited to formulate and deliver therapeutic proteins are underlined.