Degrading ciprofloxacin (CIP)-polluted water has recently emerged as an urgent environmental issue. This study introduced mechanochemical treatment (MCT) as an innovative and underexplored approach for the degradation of CIP in water. The influence of various additives (CaO, Fe2O3, SiO2, Al, and Fe) on CIP degradation efficiency was investigated. Additionally, six types of composite additives (Fe–CaO, Fe–Fe2O3, Fe–SiO2, Fe–Al, Al–SiO2, and Al–CaO) were explored, with the composite of 20% Fe and 80% SiO2 exhibiting notable performance. The impacts of additive content, pH value, and co-existing ions on CIP degradation efficiency were investigated. Furthermore, the effectiveness of MCT in degrading other medical pollutants (norfloxacin, ofloxacin, and enrofloxacin) was verified. The transformations and changes in the crystal structure, oxidation state, microstructure, and morphology of the Fe–SiO2 composite additive were characterized using X-ray diffraction, X-ray photoelectron spectroscopy, and scanning electron microscopy techniques. This study proposed a sigmoid trend kinetic model (the Delogu model) that better elucidates the MCT process. Three plausible degradation pathways were discussed based on intermediate substance identification and pertinent literature. This study not only establishes a pathway for the facile degradation of CIP pollutants through MCT but also contributes to advancements in wastewater treatment methodologies.