There is a critical need for the development of effective substance abuse and dependence treatment programs in prisons and jails. One aspect of treatment provision within this population that has received insufficient research attention is the inclusion of health promotion or wellness programs, including exercise and other health-related lifestyle modification training. Little is known about either the physiological or psychological consequences of such lifestyle modification programs among prisoners with substance use disorders. This study reports the effectiveness of an experimental wellness program included as part of a residential treatment unit in a federal correctional institute in the United States. A sample of 43 female offenders with a history of polysubstance abuse or dependence, who had volunteered to be part of a residential drug treatment program, were evaluated. Changes in health status and perceived psychological well-being between entry into the program and exit after maintaining participation for a minimum of 9 months were assessed. Pretest-posttest comparisons on a variety of physiological parameters indicated that significant improvements had occurred in the physical fitness of the group. Thematic analysis of qualitative self-reports by inmates exiting the program suggested that participants had also experienced significant enhancements in a number of areas pertaining to psychological well-being, including self-esteem, health awareness and concerns, healthy lifestyle adoption, and relapse prevention skills. These results suggest that including health promotion training in drug treatment programs for incarcerated offenders may have beneficial results.