Macrophytes have demonstrated excellent potential for the removal of pharmaceuticals from water. However, there is a lack of studies on the ecotoxicity of water after phytoremediation. In this study, we evaluated the toxicity of ciprofloxacin (Cipro) on the microalgae cells of Desmodesmus subspicatus exposed to water contaminated with Cipro and previously treated by Salvinia molesta or Egeria densa for 96 h. Microalgae exposed to Cipro (1, 10, and 100 µg L−1) in untreated water showed decreased rates of growth, respiration, and photosynthesis, and increased oxidative status (hydrogen peroxide concentration) and oxidative damages (lipid peroxidation). S. molesta exhibited a greater phytoremediation capacity than E. densa, reducing Cipro concentrations in water to below its toxic threshold to D. subspicatus (2.44 µg L−1), even when the antimicrobial was present at a concentration of 10 µg L−1. During the water treatment, neither S. molesta nor E. densa released compounds that had a toxic effect on D. subspicatus. This work demonstrates the novelty of using S. molesta and E. densa as a nature-based solution to remove Cipro from contaminated water. For the first time, we provide evidence of the ecotoxicological safety of this approach, as it prevents the deleterious effects of Cipro on photosynthetic microorganisms and helps to avoid the development of antimicrobial resistance.