Background and aims: Multiple sclerosis (MS) patients compared to healthy subjects have much higher levels of psychological disorders such as depression, anxiety and stress that greatly affect their quality of life and significant role in stimulating the onset of MS, worsening symptoms and increasing fatigue. Relaxation in complementary medicine is the most common treatments with low cost. This study aimed to determine the effects of relaxation on depression, anxiety, stress and in women suffering of MS. Methods: This study is a randomized clinical trial that was carried out on 50 patients with MS referred to MS Clinic of Kashani Hospital in Isfahan, Iran. After simple non-random sampling, participants were randomly assigned by minimization method to three groups: Reflexology, relaxation, and control groups. In the experimental group was performed relaxation intervention within 4 weeks, twice a week for 40 min and the control group were received care and routine medical treatment as directed by a doctor? Data were collected through DASS-21 questionnaire before, immediately and 2 months after interventions in two groups. Data analysis was performed by SPSS using descriptive and inferential statistics. Results: Mean scores of stress, anxiety, and depression before the intervention showed no significant difference in the two groups (P>0.5), but immediately after the intervention, independent t-test showed significant difference between mean scores of stress (P=0.001), anxiety (P=0.02) and depression (P=0.02) between groups while two months after the intervention there was only a significant difference between the mean score of stress in the two groups (P=0.003). Also, findings obtained from repeated measures analysis of variance showed that the severity stress, anxiety and depression during the different times in experimental group had significant difference (P0.05). Conclusion: It seems that relaxation technique as intervention in reducing stress, anxiety and depression is effective in women with MS. However, the technique has long-term effects on stress. So, this method as effective technique can be recommended.