A series of novel (NiAl2O4 (NAO)/NiCr2O4 (NCO)) (S1)/GL heterojunction photocatalysts, denoting as x%GL/S1 (x = 5, 10, 15 and 20), were prepared by the polyacrylamide gel method combined with low temperature sintering technique. Various characterizations confirm that there is special interfacial contact and charge transfer between NAO, NCO and GL. The 10%GL/S1 heterojunction exhibited the best photocatalytic activity and cyclic stability for the degradation of tetracycline hydrochloride (TC). Compared to NAO, NCO and NAO/NCO, the degradation efficiency of 10%GL/S1 was significantly improved, and the degradation percentage reached 83.2% within 30 min. The activity of 10%GL/S1 was studied in relation to catalyst content, drug concentration, pH value, water quality, and co-existing anion. Trapping experiments and free radical verification experiments confirmed that the holes, hydroxyl radicals and superoxide radicals played crucial roles in the photocatalysis process. Possible pathways for TC degradation were studied by HPLC-MS, and the ecotoxicity of TC and its degradation intermediates was evaluated by T.E.S.T. software. The charge transfer and photocatalytic mechanisms confirm that the introduction of GL enhances the interfacial interaction between the components, promotes the carrier migration efficiency, provides a large number of active sites for 10%GL/S1 heterojunction, and produces active free radicals after redox reaction with photoinduced electrons, effectively improving the degradation efficiency of TC.