Introduction: The use of complementary and alternative medicine (CAM) has been on the rise in recent years in the general population, as well as among patients with chronic diseases such as diabetes mellitus. The aim of this study was to add information regarding the use of CAM in patients with type 2 diabetes mellitus (DM2) in Israel and explore possible interactions between CAM and prescription medication (PM).Methods: This is a cross-sectional study based on questionnaires. The study included type 2 diabetic patients who were hospitalized in an internal medicine department at Assaf Harofeh Medical Center, Zerifin, Israel, between December 2013 and December 2014. Possible interactions between CAM and PM were evaluated by a clinical pharmacist and a clinical pharmacologist.Results: Out of 111 diabetic patients, 23.4% used CAM. There was no significant difference between the consumers and nonconsumers in terms of age, education, income, smoking, or alcohol habits. Only 11 of the 26 CAM consumers informed their physician regarding the use. We found possible drug–herb interactions in 19 of the 26 CAM consumers. A major interaction was found between omega-3 and antiaggregants and was encountered in 7 (26.9%) of the CAM consumers. Other minor and major interactions were found with vitamin E, ginkgo-biloba, co-enzyme Q10, green tea, fenugreek seeds, pyridoxine, and dandelion.Conclusions: Since CAM consumption is on the rise, it is desirable to improve our knowledge concerning their potential effects and adverse effects, especially in conjunction with PM. Given the complexity of pharmaceutics in patients with chronic diseases, among them patients with DM, the use of supplementary medicine cannot be ignored.