Subjects: Addiction is a mental disorder that affects all aspects of life, individual health, family, and society. Methamphetamine is the second widely used illegal drug in the world, and Iran has the fifth highest prevalence of methamphetamine abuse. This study was designed to assess the effectiveness of the Matrix Model interventions in improving quality of life, anxiety, and depression. Methods: This was a semiexperimental study to assess the effects of the Matrix Model interventions on quality of life, anxiety, and depression in individuals with methamphetamine dependence and their caregivers. We used the short form of the WHO quality of life questionnaire (WHOQOL-BREF), the Zung Self-Rating Anxiety Scale, and Beck Depression Inventory for data collection. Results: In total, 28 methamphetamine-dependent patients (age, 40.18 +/- 12.89 y) and 27 caregivers (age, 32.74 +/- 6.75 y) were evaluated. There was no significant differences between the patient and the caregiver group in the mean baseline scores for quality of life, depression, or anxiety (P-values, 0.79, 0.63, and 0.88, respectively). The mean scores for depression and anxiety decreased for both groups after intervention (P<0.05), whereas the mean score for quality of life increased (P<0.05). Conclusions: Matrix Model intervention is effective in improving quality of life and anxiety-depressive symptoms in patients as well as their caregivers.