This paper presents the results of a study of pigment-binder systems painted on parchment, both in the form of reference samples prepared in the laboratory, and of medieval and Renaissance illuminated manuscripts, by means of contactless Fourier-transform mid-infrared spectroscopy (FTIR). The research is aimed at validating external reflection FTIR (ER-FTIR) as a non-invasive method for the identification of paint binders in works of art on parchment. Based on a systematic FTIR investigation undertaken both in attenuated total reflection (ATR) and ER mode, we discuss the possibility to effectively discriminate between different binders, and the way in which the presence of a number of pigments can modify the spectral features of the pigment-binder system. The study reveals that gum Arabic can usually be discriminated from egg-based binders such as egg yolk and egg white, both in paintouts and in real artworks. Amongst all the pigments investigated, carbonates such as azurite and lead white are those that most significantly hinder the correct identification of the paint medium.