The ubiquitous coexistence of antibiotics and nanoplastics in aquatic environments might pose a complex threat to ecosystem and human health. However, advanced oxidation processes are promising for antibiotic remediation, the role of nanoplastics in interfering with antibiotic interfacial behavior, degradation pathways, and toxicity evolution remains unclear. This study systematically investigated the adsorption mechanisms of ciprofloxacin (CIP) onto carboxyl-modified polystyrene nanoplastics (COOH-PSNPs) and its inhibitory effect on the Fenton degradation of CIP. CIP adsorption was pH-dependent, peaking at pH 6, and followed the Freundlich model, which is attributed to the zwitterionic CIP species enabling synergistic electrostatic attraction and hydrogen bonding with the COOH-PSNPs surface, thereby facilitating multilayer adsorption. COOH-PSNPs significantly inhibited CIP degradation by scavenging hydroxyl radicals (•OH) and sequestering dissolved iron species. Natural organic matter suppressed degradation through radical scavenging and metal chelation. Density functional theory (DFT) and liquid chromatography-mass spectrometry (HPLC/MS/MS) analysis reveal four primary degradation pathways for CIP: cleavage of piperazine ring, oxidation of CC bond within the quinolone moiety, cleavage of quinolone ring, and defluorination. COOH-PSNPs not only altered the degradation pathways but also reduced intermediate diversity. Toxicity predictions indicated low acute and chronic risks for most degradation intermediates to aquatic organisms. However, several intermediates exhibited potential human neurotoxicity and enhanced blood-brain barrier permeability. Our findings reveal the critical role of nanoplastics in accumulating antibiotics and impeding their removal, providing valuable insights for environmental risk assessment of coexisting emerging contaminants.