Premenstrual syndrome (PMS) encompasses a wide variety of cyclic and recurrent physical, emotional, and behavioral symptoms that occur before menstruation and has negative impact on activities of daily living, social activities, sexual functioning and quality of life. The aim of the present study was to compare the effect of omega-3 fatty acid and perforan (Hypericum perforatum) on severity of premenstrual syndrome (PMS). This study is a triple-blind clinical trial that was carried out across three groups with 150 students after considering inclusion and exclusion criteria. The subjects of this study were randomly divided into three groups include omega-3 fatty acid group, perforan group and control (placebo) group. Every subject in this study took drugs during three subsequent cycles so they took capsules daily in the first cycle for one month and in the second and third cycles they took them from eight days before menstruation to two days after and recorded the severity of premenstrual syndrome questionnaire. Statistical analyses were performed using SPSS version 17. The repeated measures ANOVA, chi-square and Wilcoxon tests were used to compare mean differences in three groups. The data showed that there were no significant differences between 3 groups before the intervention but 1, 2 and 3 months after consumption of perforan and omega-3 capsules, the severity of PMS was significantly lower than that in control group (p<0.001). perforan and omega-3 significantly reduce the severity of PMS.