Amoxicillin (AMX) is a widely used penicillin-type antibiotic whose presence in the environment has been investigated. In this work, the degradation of the AMX in aqueous solutions by ozonation, ozonation with UV radiation (O/UV), homogeneous catalytic ozonation (O/Fe) and homogeneous photocatalytic ozonation (O/Fe/UV) was investigated. The performance results have been compared in terms of removal of amoxicillin and total organic carbon (mineralization efficiency). In all processes, complete amoxicillin degradation was obtained after 5 min. However, low mineralization was achieved. For the best available process, the potential toxicity of AMX intermediates formed after ozonation was examined using a Fish Embryo Toxicity test. Results reveal that O in alkaline solution and O/Fe/UV provide the highest mineralization rates. Ecotoxicity showed that no acute toxicity was observed during the exposure period of 96 h.