In this work, CuO doped red mud (CuO/URM) as particle electrode was applied in three-dimensional electro-Fenton (3D/EF) system for ciprofloxacin (CIP) degradation. The operating conditions of CuO/URM dosage, initial pH, applied voltage and aeration intensity were investigated in detail. The optimum degradation efficiency of CIP about 80.66% were achieved after 80 min treatment with CuO/URM dosage of 4 g/3 L, initial pH of 7, applied voltage of 10 V and aeration intensity of 5 L/min. Moreover, the effect of inorganic anions on the degradation of CIP was investigated, and it was found that Cl^- promoted the degradation of CIP, while the NO₃^-, HCO₃^-, and H₂PO₄^- had an inhibitory effect on CIP degradation. Based on the analysis of UV-Visible spectrophotometer (UV-vis) and liquid chromatograph-mass spectrometer (LC-MS), the degradation intermediates and degradation pathway of CIP in the 3D/EF system catalyzed by CuO/URM particle electrodes were proposed. Compared with the two-dimensional electrochemical (2D/E) system, 3D/EF system had more excellent removal capability of CIP and higher power energy utilization efficiency. The CuO/URM electrodes before and after use were characterized by X-ray diffraction (XRD) and Fourier transform infrared (FT-IR). It was proved that CuO/URM exhibited excellent stability. All results demonstrated that the 3D/EF system catalyzed by CuO/URM particle electrodes is a reliable technology for the disposal of CIP wastewater.