Degradation of amoxicillin (AMXL) in aqueous solution induced by contact glow discharge electrolysis (CGDE) was investigated in this paper. Experimental results demonstrated that the higher initial concentration resulted in the lower degradation rate, but the higher amount of AMXL was removed. The addition of Fe2+ or Fe3+ efficiently accelerated the degradation of AMXL. Similarly, stainless steel wire was also used as the anode in CGDE to enhance the degradation of AMXL, taking advantage of the iron ion diffused from the anode to solution. It was found that the degradation rate increased with the increasing anode diameter and anode number. Furthermore, the energy efficiency for AMXL degradation was also calculated. The energy efficiency increased with the increasing anode's diameter and decreased with the anode's number.