Lactulose and epilactose are nondigestible disaccharides with a wide range of applications in clinical medicine, nutrition, and the food industry due to their health-benefiting properties. Their chemical synthesis typically involves stringent catalytic conditions and intricate reaction procedures, resulting in elevated production costs and challenges in product separation. Cellobiose 2-epimerases (CEs) facilitate the isomerization and epimerization of lactose to produce lactulose and epilactose directly, without the need for co-substrates. This enzymatic process offers advantages such as mild reaction conditions, straightforward operation, high conversion efficiency, and reduced by-product formation. Recently, numerous CE genes have been identified and characterized, with their enzymatic properties undergoing extensive analysis. This review consolidates information on the properties of CEs from various sources and examines their catalytic mechanisms based on crystal structure data. Additionally, the current research progress in the enzymatic synthesis of lactulose and epilactose is comprehensively reviewed. The future direction of CE research is discussed, highlighting the potential for large-scale production of lactulose and epilactose through environmentally sustainable enzymatic methods.