Tetracycline (TC), a commonly utilized drug for human and animals therapy, is one of the most widespread antibiotic residues that exist in the environment. The lack of sophisticated techniques for the removal of residual tetracycline from wastewater indicates actual environmental risk. In this study, three methods for tetracycline removal from synthetic wastewater were utilized. Pillared clay was used as an adsorbent (alone) and with a coagulant (alum) in a hybrid technique. The coagulation and flocculation technique was the first method. The best operation conditions were alum dose of 2.5 mg/L, pH 7, and tetracycline concentration of 10 mg/L. The second method was the adsorption on Al-Fe pillared clay, the optimum operating conditions were found to be pH 4.5, time duration 120 minutes, tetracycline dose 90 mg/L, and the amount of Al-Fe pillared clay adsorbent 400 mg/L. In the third method (hybrid method), the optimum conditions for the above methods were used. The highest removal efficiency of tetracycline by using coagulation and flocculation only as a coagulant is 60%. While by using Al-Fe pillared clay was 90% and using the hybrid method was 94%. Thus, the hybrid technique improves the removal of tetracycline from synthesized wastewater.