The recent increase in the global consumption of antibiotics has led to faster entry of these pollutants into the environment as well as an increase in public concern about its impact on ecosystem and human health. Generally, due to high toxicity of antibiotics, biological methods are not used to treat these pollutants; therefore, advanced oxidation processes are recommended to treat and reduce the toxicity of the wastewater. In this study, we evaluated the efficacy of photo-oxidation (P) and electro-oxidation (E) processes in the removal of amoxicillin (AMX) from wastewater, either as integrated or separate processes. Moreover, the effect of variables, including current density (2-100 mA/cm2), reaction time (2-120 min), and electrolyte concentration (100-1,000mg/l) on antibiotic removal efficiency were investigated by Box Behnken design under response surface methodology, and optimal conditions were determined for pollutant removal. Then, the effect of AMX concentration and pH variables on the removal efficiency was investigated. The COD removal efficiency was also evaluated under optimal conditions, and eventually the toxicity and bioavailability of the effluent from the combined Photo-Electro oxidation process (PE) were examined. The optimal conditions for variables, including current density, reaction time, and electrolyte concentration for removal efficiency of 62.4%, were 94 mA/cm2, 95 min and 997mg/l, respectively. Investigating the Amoxicillin and pH variables showed that by reducing the contaminant concentration and pH, the antibiotic removal efficiency increased. The toxicity and bioavailability of the final effluent show the reduction of both parameters in the PE reactor effluent. The PE process can provide an appropriate function to reduce the toxicity and antibacterial properties of effluent by removing more than 60% of amoxicillin and 30% of COD from wastewater.