<p>Adequate wastewater treatment is essential for safeguarding public health and the environment by removing harmful contaminants and pollutants. This study experimentally investigated the synergistic effects of hydrodynamic cavitation (HC) and gas injection (air, oxygen, and ozone) on reducing the chemical oxygen demand (COD) of synthetic wastewater with an initial COD concentration of 8100 mg/L. The HC system was optimized at an inlet pressure of 3 bar, with gas injected into three distinct locations: the tank, the venturi throat, and the high-pressure zone before the venturi. The Results revealed that gas injection, mainly ozone, significantly enhanced COD reduction. Unlike tank injection, injection into the high-pressure zone and venturi throat achieved superior COD reductions. The highest COD reduction of 56.2% was achieved with ozone injection at 5 g/h into the venturi throat, followed by 46.3% with oxygen injection into the high-pressure zone at 10 l/min and 22.9% with air injection into the high-pressure zone at 15 l/min. Additionally, injecting gas at a distance of 40 diameters before the venturi was identified as the most effective location, ensuring adequate mixing and maximizing COD reduction. These findings underscore the critical role of strategic gas injection locations and proper mixing lengths in enhancing HC system performance and their potential to significantly improve the efficiency of wastewater treatment processes.</p>