The chronic disease burden is rapidly becoming the most significant health challenge of the 21st century. Chronic noncommunicable diseases (NCDs) are replacing infectious diseases as the most significant factor in poor global health outcomes. NCDs account for 75% of disability adjusted life years. Cancer is one of the deadliest chronic diseases and is now on the verge of overtaking heart disease as the leading cause of death in the United States. Mitochondrial dysfunction linked to nutritional imbalance, lack of physical activity, and exposure to a broad range of environmental toxins is implicated in cancer and many chronic diseases. Although nutrition and exercise recommendations have been emphasized for primary prevention, overall health remains poor due to conflicting information and the inability to easily assess adherence. The glucose ketone index (GKI) was originally developed as a quantitative point-of-care blood biomarker for assessing diet adherence in cancer therapy. However, the ratio of gluose to ketones (specifically β-hydroxybutyrate) can also be linked to the risk of chronic diseases and may help predict risk more accurately than the glucose reading alone. Low GKI ratios are hypothesized to decrease risk, while high GKI are hypothesized to increase risk. Non-insulin-compensated euglycemia may help reduce chronic inflammation, insulin resistance, and pro-tumorigenic pathways. Endogenous ketone production reduces glucose requirements while simultaneously enhancing the bioenergetic efficiency of mitochondrial energy metabolism, thus supporting metabolic homeostasis. Hence, we assert that the GKI could represent a parsimonious, individualized, and impartial biomarker for use, together with exercise and nutrition, to support therapeutic strategies to prevent and manage mitochondrial dysfunction, which contributes to cancer and many chronic diseases.