The invention discloses a synthesis method of 2-C-methyl-D-ribonic acid-1,4-lactone. The synthesis method comprises the following specific steps: step 1, isomerizing glucose in ethanol under an acidic condition to form fructose, and then enabling the fructose and N-methylbenzylamine to form fructosamine; step 2, crystallizing and purifying the fructosamine formed by the step 1 to obtain a solid; and step 3, enabling the fructosamine obtained by the step 2 to react under an alkaline condition, so as to obtain the 2-C-methyl-D-ribonic acid-1,4-lactone. According to the synthesis method disclosed by the invention, glucose is used as a raw material, so that the cost of the raw material is low; after the reaction is finished, an intermediate of the step 1 can be separated out through a crystallization manner, and a lot of uncertain impurities, generated in a glucose isomerization process, are removed, so that uncertain factors of the next step of reaction are greatly reduced; the method is simple in preparation process; conventional reaction reagents are adopted, so that the sources of the reagents are wide; and the reaction time is short, and the yield of products is high, so that the synthesis method is suitable for large-scale industrial production.