Lactoferrin (LF) is an iron-binding glycoprotein and is involved in important physiological processes. It is derived from milk and mucosal secretions. However, the separation and purification of a large amount of biologically active LF is very difficult. Therefore, technologies for synthetically manufacturing LF are urgently needed. In this review, researchers summarized the design and construction of high-expression LF synthetic biological systems. These systems are efficient and can maximize the LF production at large-scale industrial levels.