Introduction: The chronic diseases has long been great challeng in the healthcare system worldwide, with huge financial, psychological and physical costs. Given the persistence of these diseases and increased patients tendency for non-hospital care, the care processes may impact the quality of life and general health of family members, particularly the primary caregiver. The aim of this study then was to compare the effectiveness of Congnitive-behavioral Therapy, Reality Therapy and Acceptance and Commitment Therapy on quality of life, general health and coping strategies of chronic patient caregivers. Method: This study was designed and conducted as a semi-experimental study (pre-test and post-test with control group). The statistical population of this study included caregivers of people with cancer in Shohada Hospital of Tajrish and caregivers of patients with MS registered in the Tehran MS Association. A total sample of 60 subjects were selected on a voluntary basis and divided into 3 exprimental groups and a control group. All subjects were completed the General Health Questionnaire, the Coping Response Inventory, and the Quality of Life Questionnaire in the pretest and post test occations. Results: The results of this study showed that all three interventions of cognitive behavioral therapy, reality therapy and acceptance and commitment therapy could significantly impact the means of the study dependent variables compared to the control group. Cognitive-behavioral therapy interventions compared to other methods revealed more robust changes in the general health scores, quality of life, and coping strategies in caregivers. Conclusion: The effectiveness of all three interventions in cognitive-behavioral therapy, reality therapy, and acceptance and commitment therapy on caregivers public health, quality of life and coping strategies, are confirmed. The cognitive-behavioral therapy intervention is prefered compared to the other two methods, and reality therapy showed the minimum effect.