Deep involvement in the negative mood over long periods of time likely results in emotional disturbances/disorders and poor mental health. Tai Chi Chuan (TCC) is regarded as a typical mind-body practice combining aerobic exercise and meditation to prevent and treat negative mood. Although there are an increasing number of TCC studies examining anxiety, depression, and mental stress, the mechanisms underlying these negative emotions are not fully understood. Tis review study examined TCC studies related to emotional health from both clinical patients and healthy individuals. Next, several potential mechanisms from physiological, psychological, and neurological perspectives were evaluated based on direct and indirect research evidence. We reviewed recent functional magnetic resonance imaging studies, which demonstrated changes in brain anatomy and function, mainly in the prefrontal cortex, following TCC practice. Finally, the effects of TCC on emotion/mental health is depicted with a prefrontal cortex hypothesis that proposed an immune system of the mind indicating the role of the prefrontal cortex as a flexible hub in regulating an individual s mental health. Te prefrontal cortex is likely a key biomarker among the multiple complex neural correlates to help an individual manage negative emotions/mental health. Future research is needed to examine TCC effects on mental health by examining the relationship between the executive control system (mainly prefrontal cortex) and limbic network (including amygdala, insula, and hippocampal gyrus).