Objectives: To Compare the Effect of Vitamins E, B6, Calcium and Omega-3 Fatty Acids in the Treatment of Severe Mental and Physical Symptoms of Premenstrual Syndrome. Design: In this Clinical Trial, Female Students of Islamic Azad University of Sari Branch Will be Selected On the Basis of Inclusion and Exclusion Criteria of the Study and Will Fill in the Rosignol Bonlender’s Check list of the Standard Symptoms for 3 Months to Diagnose the Premenstrual Syndrome. 200 Female Patients With Moderate and Severe Forms of the Syndrome are Randomly Assigned to Five Treatment Groups. Setting & Conduct: First Group Received 1g Calcium, During Last 7 Days of the Cycle for Three Months, the Second Group Took 100 mg of Vitamin E Daily for Three Months, the Third Group Received 1 g Capsule of Fish Oil Daily for Three Months, the Forth Group Received 40 mg of Vitamin B6 Daily for Three Months, and the Last Group Received Daily One Tablet of Placebo for Three Months. In This Three Months Period, Rosignol Bonlender’s Check List of Symptoms was Also Filled. Participants With Main Inclusion and Exclusion Criteria: Single Girls With Age From 18 to 30 Years With Regular Menstrual Cycles or Cycles Between 21-35 Days Were Included in the Study. And Those Who Were Breast Feeding, Taking Hormonal Contraceptive pills, Had a History of Mental Illnesses Such as Depression, Had Traumatic Problems Within 2 Months Ago or Took Antidepressants or Herbal Within 6 Months were Excluded From the Study. Interventions: Vitamin E, Vitamin B6, Calcium, Omega-3 Fatty Acids and Placebo. Outcome Variables: Severity of Mental Symptoms, Severity of Physical Symptoms, Severity of Premenstrual Syndrome Before and After the Treatment.