Central nervous system gliomas are the most common primary brain tumor, and these are most often high-grade gliomas. Standard therapy includes a combination of surgery, radiation, and chemotherapy which provides a modest increase in survival, but virtually, no patients are cured, the overall prognosis remains poor, and new therapies are desperately needed. Tumor metabolism is a well-recognized but understudied therapeutic approach to treating cancers. Dietary and nondietary modulation of glucose homeostasis and the incorporation of dietary supplements and other natural substances are potentially important interventions to affect cancer cell growth, palliate symptoms, reduce treatment-associated side effects, and improve the quality and quantity of life in patients with cancer. These approaches are highly desired by patients. However, they can be financially burdensome, associated with toxicities, and have, on occasion, reduced the efficacy of proven therapies and negatively impacted patient outcomes. The lack of rigorous scientific data evaluating almost all diet and supplement-based therapies currently limits their incorporation into standard oncologic practice. Rigorous studies are needed to document and improve these potentially useful approaches in patients with brain and other malignancies.