Background: Psychoactive substance abuse can affect biological, psychological, social, and spiritual aspects, as well as the users’ quality of life, and obliged to carry out medical and social rehabilitation. Purpose: The purpose of the study was to identify the effect of holistic rehabilitation programs on quality of life among drug abusers. Methods: Quasi-experimental with time series design. The sample of this study amounted to 54 people, taken by G-power, all participants who will take part in the rehabilitation program at the National Narcotics Board rehabilitation clinic. Rehabilitation interventions include health assessment, psychological assessments, health counseling, human immunodeficiency virus-related voluntary counseling and testing, addiction counseling, group therapy, family therapy, client and family monitoring, relapse prevention therapy, and postrehabilitation services. Interventions are provided for 10 weeks, and delivered by health professionals. Measurement of quality of life using World Health Organization Quality of Life—Brief Version (WHOQOL-BREF) MEAT 26 statements consisting of physical, psychological, environmental, and social relationship dimensions, with an alpha value of 0.8756. The data was analyzed with the Friedman test. Results: Holistic rehabilitation influences all dimensions quality of life of drug abusers with a P-value of <0.001. Conclusions: A holistic rehabilitation program improves the quality of life of drug abusers.