Background: Distressed individuals in Korea may benefit from the practice of mind-body exercises such as Qigong. However, the effectiveness of such techniques needs to be investigated. Methods: Fifty participants who were eligible to this study were randomized into a group receiving a 4-week intervention of a brief Qigong-based stress reduction program (BQSRP) or a wait-list control group. Before and after the intervention period, saliva samples were collected and questionnaires were completed on perceived stress, anxiety, "Hwa-Byung" (anger syndrome), and quality of life. Salivary cortisol has emerged in mind-body therapy research as an easy-to-collect, relatively inexpensive, biologic marker of stress. Salivary corisol were collected to evaluate physiological effect of BQSRP. Between-group comparisons of change from baseline to study completion were analyzed by analysis of covariance for the Perceived Stress Scale and independent two sample t-tests for other measures. Results: Compared with the control group, the BQSRP intervention group displayed significantly larger decreases in Perceived Stress Scale scores (p = 0.0006), State Anxiety scores (p = 0.0028), Trait Anxiety scores (p < 0.0001), personality subscale scores of the Hwa-Byung Scale (p = 0.0321), symptoms scores of the Hwa-Byung Scale (p = 0.0196), and a significantly larger increase in World Health Organization Quality of Life Abbreviated version scores (ps < .05). Salivary cortisol levels were not changed. Conclusions: The BQSRP appears to be effective in reducing stress perception, anxiety, anger, and improving quality of life (KCT0000056).