In this study, the degradation of effluent wastewater from Penicillin G production plant by Photo- Fenton process and Ultrasound process (Sonolysis) was investigated, the effects of different process variables in both methods were evaluated and at last the degradation of Pen-G by these two processes in the optimum conditions was compared. Pen-G concentration and Chemical Oxygen Demand (COD) were selected as the environmental parameters to follow the performance of Photo-Fenton process and Sonolysis. Optimum condition of Photo-Fenton process is in H2O2/Fe2+ molar ratio 20 (20 mM H2O2 and 1 mM Fe2+) and pH 3.5 and for Sonolysis (35 KHz) is in pH 3. Complete degradation of Pen-G occurred in 30 and 70 min for Photo-Fenton process and Sonolysis, respectively. Based on the results, Photo-Fenton process is more efficient in terms of both COD degradation and Pen-G removal than Sonolysis (35 KHz).