In clinical environments, the prolonged utilization of polarization equipment can result in the accumulation of errors over extended periods. The absence of expeditious calibration techniques in clinical practice presents a significant obstacle in preserving the precision and dependability of these instruments. To address this challenge, we propose an innovative research study that presents a comprehensive calibration system specifically designed for the calibration of the backscattering Mueller matrix measurement system, enabling swift online calibration across various scenarios. This system employs an external calibration framework for real-time adjustment of the polarizer’s initial angle, overseeing the rotation of PSG and PSA motors through position measurement and control procedures, with light intensity monitored by a camera. By incorporating momentum concepts and the Adam optimization algorithm, we enhance convergence speed, mitigate noise, and improve calibration accuracy. Experimental results showcase the exceptional precision, speed, and robustness of our proposed method, achieving high accuracy and minimal error, thereby offering a promising solution for maintaining the reliability of polarization equipment in clinical settings.