The aim of this paper is to build an efficient and low-cost advanced oxidation system to realize the antibiotic wastewater purification which has a realistic significance. In this study, a system of visible light-assisted activation of natural chalcopyrite to activate periodate was adopted to remove tetracycline (TC). The results demonstrated that the removal efficiency (100% within 60 min) of TC in the CuFeS2/PI/Light system was significantly improved compared to the CuFeS2/PI system or PI process alone, and the degradation rates of TC in the CuFeS2/PI/Light system were 5.9 times higher than that of the CuFeS2/PI system, which is attributed to the synergistic effect of light and PI activation. The system also effectively degraded sodium butyl xanthate (SBX), chlortetracycline hydrochloride (CTC) and Rhodamine B (RhB), while the efficiency of the degradation process was further enhanced in natural water quality. The active substance quenching experiment revealed that [Formula: see text]OH, 1O2, O2[Formula: see text], IO4[Formula: see text] and IO3[Formula: see text] were the main substances to achieve effective TC removal. In addition, the cycling of Cu[Formula: see text]/Cu[Formula: see text] and Fe[Formula: see text]/Fe[Formula: see text] present in chalcopyrite improved the activation of PI. Further, visible light is conducive to the valence cycling of Cu and Fe, as well as the production of more oxidizing free radicals, thus achieving the synergy of photocatalysis and PI activation. This study provides a low-cost and efficient advanced oxidation pathway for the removal of antibiotic wastewater.