Cephalexin (CPX) and doxycycline (DOX) are two of the most used antibiotics to treat bacterial infections in human medicine, veterinary practices, animal husbandry, agriculture, aquaculture, among others. Nevertheless, due to their excessive consumption and incomplete absorption during their metabolization, they have been detected in different environmental matrices and the effluents of wastewater treatment plants, which reflects that conventional water treatment methods are not enough to eliminate this type of compounds. This paper presents the main results about the removal of the antibiotics CPX and DOX under low frequency (40 kHz) ultrasonic radiation (US). The effects of operational parameters such as the solution initial pH and the applied US power were assessed considering the response surface methodology and a face centered, central composite experimental design. The results indicated that evaluated operational factors significantly affect the pollutants elimination and that US technology is able to remove them completely. In addition, in terms of mineralization, experimental results showed a reduction of the organic carbon present in the solutions and a significant increase of ions (nitrates and sulfates) concentration, suggesting that part of the organic matter was transformed into CO2, H2O and inorganic species. Finally, results regarding the samples toxicity indicated that ultrasonic treatment could promote a significant reduction in this parameter, and the potential negative effect associated to CPX and DOX presence in water bodies.