<p>A photocatalytic system consisting of TiO₂ nanoparticles supported on sol-gel derived silica-titania microspheres (MICROSCAFS^®) was developed for sunlight-driven environmental remediation. This study focused on optimizing the TiO₂ nanoparticle content within the interconnected pores of MICROSCAFS^® to enhance its photocatalytic performance for the removal and degradation of the antibiotic minocycline in water, including real wastewater from a minocycline production plant. Among the various TiO₂ nominal loadings, the lowest (15 wt.%) led to the highest adsorption capacity (20%) in the dark, and to a complete photodegradation of minocycline within 30 min of solar irradiation, while unloaded MICROSCAFS^® degraded only 20% in the same period. Two by-products were identified, which are classified as being much less toxic than minocycline through in silico toxicity studies. Scavenger experiments revealed that the main contributors for the minocycline photodegradation process were superoxide ^•O₂^– radicals, boosted by visible light-driven minocycline´s sensitization, followed by ^•OH and h⁺. Photocatalytic tests on the real wastewater confirmed the system’s effectiveness, achieving 100% degradation of minocycline and by-products within 30 and 120 min of irradiation, respectively. These results highlight the potential of sol-gel derived MICROSCAFS^® as support materials for photocatalysts, offering effective and scalable solutions for water treatment applications, while facilitating the recovery and reusability of the photocatalytic nanoparticles.</p> Graphical Abstract <p></p>