To address the flow field noise problem in twin-screw air compressors, multi-physical-field coupling technology is employed to perform flow field noise calculations for the compressor. Based on the structural characteristics and noise generation principles of the twin-screw compressor, a noise reduction design method is proposed that employs a Helmholtz resonator and a three-chamber perforated muffler at the exhaust end. The muffler’s structural optimization is performed using a genetic algorithm, and the effectiveness of the noise reduction method is validated through calculations. The results indicate that the Helmholtz resonator effectively mitigates airflow pulsation at the exhaust port, stabilizing the flow and reducing low-frequency noise at the exhaust end. Additionally, the designed three-chamber perforated muffler achieves noise reduction across a broad frequency range. With this noise reduction method, the exhaust port noise of the twin-screw compressor is reduced from 100–114 dB to 37–68 dB. These findings provide valuable insights for vibration and noise reduction in twin-screw air compressors.