Objective: Multiple sclerosis is a chronic, progressive neurological disease that, due to its special nature, has various physical and mental influences on the patients and their family's lives, decreasing the quality of life and threatening the meaning of life. The purpose of the present study was to evaluate the effectiveness of the group hope therapy training on the quality and the meaning of life in patients with multiple sclerosis and their family caregivers. Method: This quasi-experimental study was performed using pretest-posttest and control group. Thirty patients with multiple sclerosis along with 30 family caregivers who got low to medium scores on the Meaning in Life questionnaire by Steger (MLQ), Multiple Sclerosis Impact Scale (MSIS-29), and the Iranian Quality of Life questionnaire (IRQOL) for the caregivers were selected purposively. Then, the patients were randomly divided into two groups of 15 individuals in experimental and 15 individuals in control groups. The caregivers were grouped in the same manner. The protocol of group hope therapy training was carried out through eight two-hour sessions in two weeks separately on two experimental groups (the patients and the caregivers), and finally the posttest was given to four experimental and control groups. Results: The results of the data showed that the meaning of life in both the patient and the caregiver experimental groups increased significantly (P < 0.001), but there was no significant change in the patient and the caregiver control groups. Conclusion: Group hope therapy training is an effective intervention for improving the meaning of life and the quality of life in patients with multiple sclerosis. Also, any psychological intervention that aims to improve the quality of life in patients in an advanced stage of the disease requires attention to both the physical and the mental issues at the same time. Although group hope therapy training has improved the meaning of life in such patients, it did not have a significant impact on the quality of life. Therefore, paying attention to the stages of multiple sclerosis and the physical condition of the patients during the therapeutic intervention and adopting necessary complementary interventions seems to be essential.