Although water contamination with drug residues is a threat to public health, there are currently barely any effective methods of purifying water from pharmaceutical substances. In this study, continuous-flow sonoplasma treatment was used for the complete degradation of tetracycline and ciprofloxacin in polluted municipal water. The addition of CeO2 nanoparticles as catalysts significantly increased the degradation rate of the antibiotics, and а degradation degree of 70% was achieved. The presence of reactive oxygen species in the CeO2-nanoparticle-containing sonoplasma-treated system was experimentally proven for the first time using the chemiluminescence technique.