Elevated circulating erythritol is a predictive biomarker of weight gain, type 2 diabetes mellitus, and cardiovascular disease. In individuals with existing cardiometabolic disorders, elevated erythritol is also associated with comorbid conditions. Erythritol is a sugar alcohol that is found naturally in fermented foods and is regularly used as a nonnutritive sweetener. In addition to the diet, erythritol can be derived endogenously in mammals from glucose through the pentose phosphate pathway. This dissertation explores the role of both dietary and endogenous erythritol in the progression of cardiometabolic diseases. We observed that chronic exposure to dietary erythritol had no impact on weight and adiposity or glucose tolerance in mice. This was true in mice exposed to low-fat diet or an obesogenic high-fat diet. We then focused on the dietary and intracellular factors that regulate the endogenous synthesis of erythritol. We identified that glucose availability and reactive oxygen species both promote endogenous erythritol synthesis in cell culture models. In addition, erythritol synthesis from glucose is regulated by non-oxidative pentose phosphate enzymes in cultured cells. We observed that the enzymes sorbitol dehydrogenase (SORD) and alcohol dehydrogenase 1 (ADH1), both of which catalyze the final step in the conversion of glucose to erythritol, were not essential for erythritol synthesis in mice. Finally, we found that diet-induced obesity and glucose intolerance did not impact endogenous erythritol synthesis in mice. High sucrose intake, however, elevated circulating erythritol levels and kidney and skeletal muscle erythritol content. We concluded that erythritol synthesis and excretion may be an additional mechanism to dispose of glucose when it is consumed in excess.