In support of NASA’s plan to establish human settlements on the Moon and Mars in the near future and the emergence of cutting-edge artificial intelligence as a tool for better health care, we look for ways to help astronauts stay physically and mentally healthy during a long and stressful trip. After reviewing existing aerobic and strength exercise methods available to astronauts, we propose that traditional Tai Chi Chuan (TCC) or Taijiquan can serve as a non-invasive intervention to help astronauts maintain physical and physiological integrity and cope with the impact of microgravity during and after spaceflights. Biomechanical aspects of TCC in terms of neuromuscular and musculoskeletal conditions are presented based on a review of evidence from the scientific literature that defines physiological responses associated specifically with the practice of TCC as relevant to space mission-related effects of microgravity on human physiology. This article provides a comprehensive review and description of the TCC biomechanics and their health influences in microgravity. The mysterious Chi (or Qi) of TCC is scientifically defined as kinesthetic sensations of position, movement, and force of muscles, tendons, and joints throughout body segments in kinetic chain motions. These sensations can be used to judge the correctness of TCC trainings as a countermeasure against microgravity to improve proprioception, kinesthesia, and mind-body coordination for astronauts. This study has far-reaching implications for the integration of TCC practices in complement with the effectiveness of existing countermeasure approaches, and provides direction for future research that might bridge the knowledge gap in improving exercise countermeasures for human spaceflight.