The solubility of small molecules in a polymer and the consequent glass transition temperature reduction of the polymer with a plasticizing effect are two of the most important thermodynamic properties of small molecule polymer systems. In this study, with an improved dual QCM device and corresponding method for determination, the solubilities of CO2 in poly(methyl methacrylate) (PMMA) film, ibuprofen (mu) in supercritical carbon dioxide (SCCO2), and the CO2/IBU compound into PMMA film at different temperatures and pressures were determined, respectively, and then the solubility of IBU in PMMA film was calculated according to the theory of infinite dilute solution. Both CO2 and IBU molecules can plasticize the polymer in CO2 polymer and drug polymer systems. For the CO2 IBU PMMA ternary system, the glass transition temperature reduction behavior of PMMA versus the pressure of CO2 and proportion of IBU in PMMA was investigated, which would illustrate the synergistic plasticizing effect of CO2 and IBU on the glass transition temperature of PMMA.