In the present work, the influence of the divergent section angle of hydrodynamic cavitation (HC) devices on melanoidin degradation was investigated. The HC reactor was operated alone and in combination with an oxidant at four concentrations of H2O2: 0.9, 2.8, 4.7, 6.6 g L−1. Five Venturi devices (with divergent angles of 4°, 8°, 11°, 14°, and 90°) were made and analyzed at five operating pressures (150, 300, 440, 600, 760 kPa) for a period of 30 min. ANOVA and Fisher's LSD method were used to define the best angle and the best operating pressure for melanoidin degradation. The highest efficiency of melanoidin degradation (14.32 %) was obtained with an angle of 11° and a pressure of 600 kPa. Computational Fluid Dynamics (CFD) simulations were performed to study the influence of the divergent angle on the flow parameters. They showed that at smaller angles (4° and 8°) there was an excess growth of cavities, increasing the chance of coalescence of cavities and reducing the intensity of collapse. On the other hand, at a very high angle (90°), the cavities collapsed before growing, releasing less energy at the time of implosion. The degradation efficiency increased to 60.84 % when 2.8 g L−1 of H2O2 was applied to the HC reactor, at pH 2.5. Higher concentrations of H2O2 reduced the degradation efficiency, indicating a “scavenging” effect in combined systems (HC + H2O2) due to the generation of unreactive radicals. The present study demonstrated that the combination of HC + H2O2 is a promising alternative for melanoidin degradation, with the divergent angle of the device being an important parameter of this treatment process.