As an essential vitamin for the human folic acid functions as a carrier of one-carbon units and participates in various metabolic reactions. A deficiency in folic acid can lead to an increased risk of fetal neural tube defects megaloblastic anemia and cardiovascular diseases and depression. Both red blood cell folate and serum folate are indicators of the body's folate levels. Red blood cell folate reflects the body's folate storage status over the past 3 months and avoids the dietary intake. Plasma folate monitoring is a faster and more convenient method. In different disease prevention and treatment contexts the association between red blood cell folate and serum folate levels and the diseases themselves is inconsistent and even contradictory which results in no consistent conclusion regarding their application value. Excessive supplementation of folic acid can also increase the risk of certain diseases making it necessary to choose appropriate indicators to reflect the body's folate levels. This article reviews the applications of red blood cell folate and serum folate measurements in the prognoses of congenital abnormalities cardiovascular diseases megaloblastic anemia and depression. It also summarizes the hazards of excessive folic acid supplementation aiming to provide reference guidelines for selecting suitable indicators for the prevention and treatment of related diseases.