The brain remains mostly fatal, highlighting the need for innovative treatments despite improvements in the surgery, radiation, and chemotherapy. The blood-brain barrier, redundant molecular pathways, and genetic heterogeneity have all hampered the utility of molecularly targeted drugs. As an therapeutic option and to reduce the symptoms, the frequency of Complementary and alternative medicine (CAM) has been increasing in brain tumors. CAM is operationally defined as any practice that aims at cure or at obtaining similar effects as evidence-based medicine, but without scientific evidence and without clinical trial data to support efficacy and safety. Mostly used type of CAM was biological base therapies including the herbal, diet supplementary, vitamin and minerals. The factors affecting use of CAM ARE the duration/situation of disease, educational level and history of CAM usage in society. In this chapter, a summary of CAM used as a targeted therapy for patients with glioblastoma is presented along with information on in vivo and in vitro studies and potential future therapeutic approaches.