This study investigates the removal of diclofenac from water by adsorption onto a dealuminated Y-type zeolite (DAY), followed by destructive regeneration of the spent adsorbent using homogeneous advanced oxidation processes. Two oxidation systems were evaluated: the Fenton reaction ( \(\text {HO}^{\bullet }\) ) and thermally activated peroxodisulfate (SO \(_{4}^{\bullet -}\) ). For the Fenton process, two catalysts were tested: ferrous ion (Fe \(^{2+}\) ) and the Fe(II)–EDDS complex, using ethylenediamine-N,N′-disuccinic acid as a chelating agent. The influence of the oxidation process and of the localization of radical generation on regeneration efficiency was assessed. Regeneration performance was quantified by the adsorption capacity recovery ratio ( \(q_0/q_{0,1}\) ) obtained from Langmuir isotherm modelling. The results show that adsorbent regeneration is feasible over several adsorption-regeneration cycles, but that the recovered adsorption capacity decreases with cycle number. For Fenton regeneration with Fe \(^{2+}\) , the adsorption capacity recovery was 71.9% after the second cycle and decreased to 19.8% after the third. In contrast, thermally activated peroxodisulfate yielded higher regeneration efficiencies, with 91.1% and 50.5% recovery after the second and third cycles, respectively, which is attributed to the greater persistence of SO \(_{4}^{\bullet -}\) and its ability to oxidize adsorbed diclofenac within the zeolite pores. When the Fe(II)–EDDS complex was used at pH 3, the regeneration rates increased to 75.2% (second cycle) and 39.1% (third cycle), and at pH 7, the Fe(II)–EDDS complex further improved adsorption capacity recovery. Overall, immobilizing the Fe(II)–EDDS catalyst on the zeolite surface enhances regeneration efficiency for DAY.