Fluoroquinolone (FQ) derivatives with environmental friendliness regarding photodegradation, bioconcentration, and genotoxicity were selected from our previous works so that their transformation pathways of biological metabolism, photodegradation, microbial degradation, and chlorination disinfection could be studied. The pathways of these molecules and their derivatives were simulated to investigate the genotoxicity of their transformation products. The results showed that the genotoxicity of the biological metabolites, photodegradation products, and microbial degradation products of the maternal FQ derivatives partially increased, whereas the disinfection by-products exhibited lower genotoxicity than their precursors. Some designed FQ molecular derivatives still had potential environmental risks in biological metabolism, photodegradation, and microbial degradation. This study demonstrated that it is necessary to take into account the potential environmental risks of the transformed products of the modified FQs molecules during biometabolism, photodegradation, microbial degradation, and chlorination processes when designing novel FQ molecules. In future studies, assessing the potential environmental risks during various artificial or natural processes can be applied to screen environmentally friendly novel FQ molecules to avoid and or reduce their threat to environmental and human health.