In this study, the effect of UV treatment on the physicochemical properties and structural variation of metal oxide-silica nanocomposites (Mn2O3-Fe2O3@SiO2) has been investigated. Based on the results, UV irradiation significantly affects the nanocomposite structure, where SiO2 network reconfiguration, change in surface OH group density, and surface area were observed. Erythromycin (ERY) has been chosen as a module pollutant to compare the performance of the pristine and UV-treated nanocomposites. The pristine nanocomposite had a high adsorption efficiency (99.47%) and photocatalytic activity (99.57%) at neutral pH for ERY in the first cycle, and this efficiency decreased significantly for the multiple cycles. However, different results have been observed for the UV-treated nanocomposite, where it retained its performance for ten consecutive cycles. This enhanced performance is attributed to the structural modifications after UV exposure, where increased surface area, pore volume, and OH group density resulted in an increased number of the possible mechanisms responsible for the adsorption/oxidation of ERY. Moreover, oxidation of adsorbed molecules by UV light after each cycle can also be another reason for enhanced removal. For the first time, the fate of ERY is studied using regenerated nanocomposites after the last cycle. LC/MS/MS results showed that ERY degraded in 20 min, and the produced reaction by-products were adsorbed by nanocomposites. This study could be a foundation research for the practical approaches for the regeneration of nanomaterials and the successful removal of organic pollutants from aquatic environments.