This study presents a novel hybrid approach integrating hydrodynamic cavitation (HC) with advanced oxidation processes (AOPs) like hydrogen peroxide (H2O2) and ozone (O3) to enhance the biodegradability of real dairy industry wastewater. The research focuses on optimizing HC with other oxidants and exploring the synergistic effects of oxidants on pretreatment efficacy. Experimental investigations were conducted using an orifice plate HC reactor at 2 bar inlet pressure, treating actual dairy effluent with high chemical oxygen demand (COD) and low initial biodegradability index (BI = 0.35). HC treatment alone improved the BI to 0.66, while combining HC with H2O2 (9 g/L) and combining with O3 (200 mg/h) further increased the BI to 0.74 and 0.81, respectively. Most notably, the ternary combination of HC + H2O2 + O3 achieved a substantial increase in BI to 0.89, demonstrating a strong synergistic effect. This enhancement is attributed to the intensified generation of reactive hydroxyl radicals (.OH) through cavitational and oxidative reactions, leading to effective degradation of complex organic pollutants and improved downstream biological treatment potential. These results underscore the viability of HC-AOPs hybrids as cost-effective and sustainable pretreatment strategies for dairy wastewater management.