The objective of this work was to study the interactions between a model drug, sodium diclofenac (SDCF), and ureasil–poly(ethylene oxide) (PEO) hybrid materials, aiming to understand and to optimize the drug delivery behaviour. Ureasil–PEO hybrids obtained by the sol–gel process and containing short (PEO500) and long (PEO1900) polymer chains were prepared. Differential scanning calorimetry (DSC), Raman spectroscopy and ²⁹Si NMR were used to investigate the interactions between SDCF and the hybrid matrix. The decrease in melting temperature of the semi-crystalline PEO1900 hybrid from 30.1 (SDCF-free matrix) to 22.3 °C (SDCF-loaded matrix) and the decrease of the T_g values of about −3 °C in SDCF-loaded PEO500 matrices associated to the Raman results confirm the interactions between SDCF and the PEO chains of the hybrid matrix. The role of the coexistence of crystalline and amorphous hybrid phase was clearly evinced by the bimodal drug release pattern achieved for the PEO1900 matrix.