In Islamic teaching, the communication with God and remembering Him is considered a factor for mental unlocking and transcendence, which causes much psychological and health effects; religious and Islamic teachings particularly affect people's health. The present study was conducted with the aim to determine effect of Islamic-based spiritual therapy on mental health and self-esteem in addicts. This is an experimental pretest-posttest study with trial and control groups. This is an experimental pretest-posttest study with trial and control groups. Study population consisted of addicts from a methadone-therapy addiction treatment center. The sample size initially included 90 randomly selected addicts from the mentioned center, of whom 40 were chosen from those that scored the lowest in self-esteem questionnaire and highest in mental health questionnaire, and were then randomly divided into trial and control groups. The trial group received nine 2-hour sessions of spiritual therapy, but the control group received no intervention. Data were collected using the goldberg's general health questionnaire-28 and coopersmith's self-esteem inventory, and analyzed using covariance analysis. The results obtained confirmed effectiveness of spiritual therapy with emphasis on Islamic teachings in improving self-esteem and mental health of addicts.