2St. John’s Wort (Hypericum perforatum L.) is a widely utilized antidepressant plant, which has been used as both therapeutic drug and over-the-counter (OTC) product in all around the world. There are many ethnomedical, experimental, and clinical studies demonstrating its antidepressant activities. It seems to be quite effective on the treatment of mild-to-moderate depression, as reported in various controlled clinical trials. In addition to its well-known antidepressant activities, St. John’s Wort has been reported to be used in folkloric medicine for the cure of diabetes mellitus. We have previously reported that extracts of aerial parts of H. perforatum normalize blood glucose and pain perception and depression/anxiety levels in streptozotocin (STZ) diabetic rats.

On the other hand, clinical management of depression is a dilemma in diabetic patients. Most of antidepressant agents may interfere with glycemic controls by increasing or decreasing blood glucose levels in depressive patients with diabetes mellitus. On the other side of this clinical problem, there are drug–drug interactions interfering both antidepressant and antidiabetic treatments. Hence, preparations of St. John’s Wort seem to be most appropriate cure for the diabetic patients having mild-to-moderate depression.