The three-dimensional flow and mass transfer conditions in 5 L and 40 L airlift oscillation loop reactors were studied and compared with existing two-dimensional simulation and experimental data to verify the accuracy of the method. Then, the fluid dynamics behavior of the 2500 L reactor was simulated via supercomputing and provided guidance for production data. The results indicate that the application of oscillation operation in the 40 L multi-guide tube reactor can effectively improve the gas holdup and mass transfer coefficient in the reactor, with a maximum increase of 38% and 29%. For the 2500 L multi guide tube reactor, oscillation operation oscillation operation can significantly improve gas holdup and mass transfer coefficient increase gas holdup by 46% under 0.5 vvm operating conditions; the mass transfer coefficient increased by 54%. Therefore, oscillation operation can greatly improve the mass transfer coefficient for actual production reactors. After digging a hole in the middle sleeve, the circulating liquid speed has no effect. Although the gas holdup and mass transfer coefficient decreased by 1.3%, the gas holdup inside the entire reactor was more uniform, effectively reducing the average bubble aggregation.