Introduction: Present research attributions mapped at the comparative scrutiny of Acceptance and Commitment Therapy (ACT) and Cognitive Behavior Therapy (CBT) impacts on depression amongst the Multiple Sclerosis (MS) patients. Methods: Present study counted as a clinical trials or treatment trials with pretest, post-test and also 1. 5 months phase follow up by use of input criteria and neurologist expert from [that for] sample selection population [MS patients] after the list preparation of an outpatient clinic of Baqiyatallah hospital visitors and call on them, 30 persons with regard to the downsizing and reduction of them, selected via convenience sampling method and randomly put in order as two control groups and one group with no therapy. the used material were; Depression, Anxiety and Stress Scale-21 DASS-21 that face-to-face completed by two experimented groups in pre-therapy (pretest), after-therapy (post-test) and 1. 5 months two follow up (afterthought) phases and finally participants considered 30 patients. Then; the first experimental group received 60 minutes Acceptance and Commitment Therapy (ACT) per 8 sessions particularly/ especially chronic pain and the second one; received 60 minutes Cognitive Behavior Therapy (CBT) per 10 sessions, also following along with outcomes analyzed and scrutinized by use of variance and co-variance analysis. Results: outcomes showed that Acceptance and Commitment Therapy (ACT) and Cognitive Behavior Therapy (CBT) with a little difference and as the same lead/cause to progression and improvement of depression amongst the Multiple Sclerosis (MS) patients. Conclusion: results indicated that Acceptance and Commitment Therapy (ACT) and Cognitive Behavior Therapy (CBT) as same as the other can effective on progression and improvement of depression amongst the Multiple Sclerosis (MS) patients.