Tuberculosis, caused by Mycobacterium tuberculosis (M.tb), remains the biggest infection burden in the word. Rifampin (RIF) and Isoniazid (INH) are the most effective antibiotics for killing M.tb. However, the resistance rate of rifampin and INH are high and lead to almost 35% treatment failure. Metformin enhanced anti tuberculosis efficacy in killing M. tuberculosis through several mechanism, firstly through autophagia mechanism and secondly by activating superoxide dismutase (SOD). Metformin activated mTOR and AMPK then induced more effective autophagy against M.tb. Superoxide Dismutase (SOD) is an enzyme produced in the host’s antioxidant defense system. SOD neutralizes reactive oxygen species (ROS) that excessively produced during phagocytosis process against M.tb. Excessive production of ROS associated with Th1 overactivation and leads into macrophage activity inhibition and excessive tissue damage. Metformin has ability in improving SOD level during inflammation.