The pharmaceutical drug naproxen was loaded in three different silica hosts with pore diameters of 2.4 (MCM), 3.2 (MCM), and 5.9 nm (SBA), respectively: napMCM-2.4nm, napMCM-3.2 nm, and napSBA-5.9 nm. To access the guest physical state in the prepared composites, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and attenuated total reflectance Fourier transform infrared spectroscopy were used. The different techniques provided complementary information on a molecular population that was revealed to be distributed among different environments, namely the pore core, the inner pore wall, and the outer surface. It was found that naproxen is semicrystalline in the higher pore size matrix being able to crystallize inside pores; after melting it undergoes full amorphization. In the case of the lower pore size matrix, naproxen crystallizes outside pores due to an excess of filling while most of the remaining fraction is incorporated inside the pores as amorphous. Crystallinity in these two composites was observed by the emergence of the Bragg peaks in the XRD analysis, whereas for napMCM-3.2 nm only the amorphous halo was detected. The latter only exhibits the step due to the glass transition by DSC remaining stable as amorphous at least for 12 months. The glass transition in the three composites is abnormally broad, shifting to higher temperatures as the pore size decreases, coherent with the slowing down of molecular mobility as probed by dielectric relaxation spectroscopy. For napSBA-5.9 nm the dielectric response was deconvoluted in two processes: a hindered surface (S-) process due to molecules interacting with the inner pore wall and a faster α-relaxation associated with the dynamic glass transition due to molecules relaxing in the pore core, which seems a manifestation of true confinement effects. The drug incorporation inside a nanoporous matrix, mainly in 3.2 nm pores, was revealed to be a suitable strategy to stabilize the highly crystallizable drug naproxen in the amorphous/supercooled state and to control its release from the silica matrix, allowing full delivery after 90 min in basic media.