Abstract Swainsonine (1) belongs to the family of indolizine alkaloid with strong neurologically toxic effects on herbivorous livestock. Recently, a great amount of evidence confirmed that this alkaloid displayed a wide range of bioactivities especially anti-cancer biological effects. The potential targets of swainsonine (1) were now revealed to be the mannosidase and Golgi mannosidase II. Its low yield in plants or fungi, and no economically total synthesis route in practice as the key bottleneck restricted its further structure-activities relationships (SAR) investigation in drug discovery. This mini-review highlighted the biosynthetic advance of swainsonine (1) from 1973 to 2017 based on the results of isotope-labelled experiments and the recent research of its biosynthetic gene cluster, which could provide some thoughts for further biosynthetic investigation and efficiently biomimetic synthesis of swainsonine (1) in order to increase its output in practice.