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The widespread use of antibiotics has increased their presence in wastewater, largely due to inadequate removal by conventional treatment methods. This highlights a critical need for effective degradation strategies to mitigate environmental and public health risks. This study reports the photocatalytic degradation of amoxicillin (AMX) using calcium zinc hydroxide dihydrate [CaZn 2 (OH) 6 ·2H 2 O] (CZ) and zinc oxide (ZnO) nanoparticles (NPs) synthesized by different routes. X-ray diffraction results confirmed the formation of CZ NPs with an 81-95% crystalline phase, while ZnO NPs present a single crystalline phase. The photolysis of AMX under UV-A light (365 nm) was strongly pH-dependent, with degradation rates of 34.7, 5.7, and 4.2% observed at pH 3, 5, and 13, respectively. Maximum adsorption occurred at pH 3, with ZnO achieving 63-83.2% AMX removal and 23.5-47.1% in the case of CZ. The highest overall AMX removal was observed at pH 3, where adsorption dominated the photocatalytic process for both CZ and ZnO. At pH 5 and 13, degradation was primarily driven by photocatalysis in CZ materials, particularly CZ-HT and CZ-SG, while adsorption remained predominant in ZnO. Proton nuclear magnetic resonance analysis indicates benzene ring cleavage in AMX photodegraded by CZ materials. Furthermore, the residues of photodegraded AMX by CZ materials lost antimicrobial activity against Gram-positive and Gram-negative bacteria. Additionally, the reuse of NPs over four cycles maintained consistent degradation performance, highlighting their potential for repeated applications. The comparative analysis of CZ and ZnO NPs superior photocatalytic efficiency of CZ in degrading AMX. This efficiency, along with its potential for repeated use, establish CZ as a promising material for environmental applications aimed at reducing antibiotic contamination and the associated risks of resistance development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)