Erythritol (1,2,3,4-butanetetrol) is a non-caloric c4 polyol made by fermentation that has a sweetness 60–70% that of sucrose. The safety of erythritol has been consistently demonstrated in animal and human studies. Erythritol has a higher digestive tolerance compared to all other polyols because about 90% of the ingested erythritol is readily absorbed and excreted unchanged in urine. Erythritol is used in a wide range of applications for sweetening and other functionalities, e.g., in beverages, chewing gum and candies. In this review, we summarise the health effects of erythritol described in the literature. We focus on studies involving the anti-cariogenic and endothelial protective effects of erythritol. We conclude that erythritol could be of great importance and could be considered to be the preferred sugar substitute for a rapidly growing population of people with diabetes or pre-diabetes to reduce their risk of developing diabetic complications.