The preparation, characterization, and in vitro release of 5-aminosalicylic acid (5-ASA) from methacrylic acid (MAA)/perlite composites (APC) prepared via a sol-gel route are reported. The free-radical graft polymerization of methacrylic acid (MAA) onto perlite particles was studied experimentally. The grafting procedure consisted of surface activation with 3-(trimethoxysilyl) propyl methacrylate (TSPA), followed by free-radical graft polymerization of methacrylic acid (MAA) in ethyl acetate with 2,2'-azobis-isobutyronitrile (AIBN) initiator. The composition of the composites hybrid materials was determined by FTIR spectroscopy. Equilibrium swelling studies were carried out in enzyme-free simulated gastric and intestinal fluids (SGF and SIF, respectively). The dried composites were immersed in a saturated solution of 5-ASA in water overnight and dried over a period of three days at room temperature and the in vitro release profiles were established separately in both (SGF, pH 1) and (SIF, pH 7.4). The 5-ASA concentration of the solution was measured using a UV-Vis spectrophotometer (205 nm) at different time intervals. The in vitro drug release test revealed that the release rate of 5-ASA in buffer solutions increased with the silica content in the composites; on the contrary, the increase of the content of 3-(trimethoxysilyl) propyl methacrylate (TSPA), a coupling agent, decreased the drug release rate.