The purpose of this research is to investigate the effectiveness of cognitive-behavioral group therapy in mental health and prevention of relapse in drug-dependent people. In this quasi-experimental study, 112 individuals who have started Methadone treatment in the two Drug-Abuse Treatment Centers in Tehran are divided into an experimental (56 subjects) and a control (56 subjects) group. The experimental group undergoes 12 90-minute sessions of cognitive-behavioral group therapy and the control group does not receive any particular treatment. All participants complete the General Health Questionnaire (GHQ-28) and undergo urine tests for morphine at the beginning of the study, at the end of the cognitive-behavioral group therapy and two months after the completion of treatment. The data are analyzed using descriptive statistics, χ2, Post hoc test and multiple analysis of variance. The MANOVA data analysis shows a significant difference between the two groups regarding the mental health in the post-test stage (p<0. 001). χ2 test results indicate significant difference in the rate of relapse in the two groups (p<0.001). As a result, cognitive behavioral group therapy is effective in the improvement of general health and prevention of relapse in drug- dependent individuals.