Simple SummaryAfter calving, the milk production of dairy cows increases rapidly, but the nutrient intake cannot meet the demand for milk production, forming a negative energy balance. Dairy cows in a negative energy balance have an increased risk of developing clinical or subclinical ketosis. The ketosis in dairy cows has a negative impact on milk production, dry matter intake, health, immunity, and reproductive performance. Propylene glycol can be used as an important gluconeogenesis in ruminants and can effectively inhibit the formation of ketones. Supplementary propylene glycol to dairy cows during perinatal is an effective method to alleviate the negative energy balance. This review summarizes the reasons and consequences of negative energy balance as well as the mechanism and effects of propylene glycol in inhibiting a negative energy balance in dairy cows. In addition, the feeding levels and methods of using propylene glycol to alleviate negative energy balance are also discussed.With the improvement in the intense genetic selection of dairy cows, advanced management strategies, and improved feed quality and disease control, milk production level has been greatly improved. However, the negative energy balance (NEB) is increasingly serious at the postpartum stage because the intake of nutrients cannot meet the demand of quickly improved milk production. The NEB leads to a large amount of body fat mobilization and consequently the elevated production of ketones, which causes metabolic diseases such as ketosis and fatty liver. The high milk production of dairy cows in early lactation aggravates NEB. The metabolic diseases lead to metabolic disorders, a decrease in reproductive performance, and lactation performance decline, seriously affecting the health and production of cows. Propylene glycol (PG) can alleviate NEB through gluconeogenesis and inhibit the synthesis of ketone bodies. In addition, PG improves milk yield, reproduction, and immune performance by improving plasma glucose and liver function in ketosis cows, and reduces milk fat percentage. However, a large dose of PG (above 500 g/d) has toxic and side effects in cows. The feeding method used was an oral drench. The combination of PG with some other additives can improve the effects in preventing ketosis. Overall, the present review summarizes the recent research progress in the impacts of NEB in dairy cows and the properties of PG in alleviating NEB and reducing the risk of ketosis.