Introduction. Evidence had proven the positive effect of exercise therapy for illicit drug abusers. However, the effectiveness of exercise for ketamine abusers, who were dominant in Hong Kong, was unknown. Objective. To evaluate the effect of structured exercise program for health and relapse prevention for rehabilitees in Drug Treatment and Rehabilitation Centers (DTRCs) in Hong Kong. Methodology. Following the baseline assessments on physical fitness, mental health, cognitive function and relapse risk, all subjects received an 8-week aerobic kickboxing training followed by post-exercise reassessment. Results. From September to December 2013, 23 female subjects with mean age of 22.8 years (SD 3.0) were recruited. Among all subjects, 74% with drug abused for 5 years or more. Poly-substance abusers accounted for 91.3%; in which 78.3% were ketamine abusers. For baseline assessment, the risk of central obesity increased by 34.6% for subjects admitted to DTRCs for more than 3 months (p = 0.110). For the post-exercise evaluation, significant improvements were reported on waist circumference (29.6 to 28.5 inches; p = 0.000), peak flow rate (340 to 380 L/min; p = 0.001), sit-up (17 to 22 repetitions; p = 0.000), sit-and-reach (31 to 37 cm; p = 0.001), hexagon jump test (26.0 to 20.8 sec; p = 0.000) and agility ladder test (p = 0.000). The cardiovascular fitness was improved from 40.6ml/kg/min to 42.3ml/kg/min (p = 0.073) after training. For mental health, 30.4% of the subjects showed moderate to severe depression in Beck Depression Inventory (BDI) and 21.7% showed anxiety disorder in Hospital Anxiety and Depression Scale- Anxiety subscale (HADs-Anx). BDI significantly reduced from 14.3 to 10.5 (p = 0.046) and HADS-Anx reduced from 8.3 to 6.1 (p = 0.101) after training. For cognitive function assessed by CANTAB tests, 78.3% and 64.3% of the subjects failed episodic visual memory and visual sustained attention tests respectively. Significant improvement in visual memory (p = 0.018) and an overall improvement in spatial planning (p = 0.202), rule acquisition and attentional set shifting (p = 0.147) were revealed. For relapse prevention, significant improvements in Stimulant Relapse Risk Scale (64.4 to 56.2; p = 0.01) and contemplation stage (7.8 to 8.3; p = 0.001) were found. Conclusion. Exercise therapy was shown to have a merit for substance abuse rehabilitation, including ketamine abusers.