In the 1870s, dentures were one of the first products made with celluloid, the first semi-synthetic plastic. Despite the significance of denture development in the history of celluloid and plastics, the chemical characterization of dentures in museum collections has never been attempted. It is urgent to assess the extent of celluloid heritage in denture collections due to the high degradation risk that this material imposes. In this work, 21 dentures from the National Museum of American History and from the Dr. Samuel D. Harris National Museum of Dentistry were characterized using a multi-analytical methodology using handheld Raman, X-Ray fluorescence, and micro-Fourier transformed infrared spectroscopies. All dentures were successfully characterized: 12 are made of celluloid, 4 of vulcanized rubber, 2 of phenol–formaldehyde, 2 of polyvinyl chloride—polyvinyl acetate copolymer (PVC-PVAc) and 1 of polymethyl methacrylate (PMMA). The identification of the dentures’ base materials allowed a better understanding of their history and posed new questions about their conservation. Handheld Raman was demonstrated as an excellent in-situ tool for the study of polymeric materials.