A degradation study of diazepam (DZP) in aqueous media by gamma radiation, high frequency ultrasound, and UV radiation (artificial-solar), as well with each process intensified with oxidizing agents (H2O2 and Fenton reagent) was performed. The parameters that influence the degradation of diazepam such as potency and frequency, irradiation dose, pH and concentration of the oxidizing agents used were studied. Gamma radiation was performed in a 60Co source irradiator; an 11 W lamp was used for artificial UV radiation, and sonification was performed at frequency values of 580 and 862 kHz with varying power values. In the radiolysis a 100% degradation was obtained at 2500 Gy. For the sonolysis, 28.3% degradation was achieved after 180 min at 862 kHz frequency and 30 W power. In artificial photolysis, a 38.2% degradation was obtained after 300 min of UV exposure. The intensification of each process with H2O2 increased the degradation of the drug. However, the best results were obtained by combining the processes with the Fenton reagent for optimum H2O2 and Fe2+ concentrations, respectively, of 2.95 mmol L−1 and of 0.06 mmol L−1, achieving a 100% degradation in a shorter treatment time, with a dose value of 750 Gy in the case of gamma radiation thanks to increasing in the amount of free radicals in water. The optimized processes were evaluated in a real wastewater, with a total degradation at 10 min of reaction.