Lactobacillus fermentum has been used in industrial processes and food fermentation for a long time. Because it is of human origin, non-pathogenic, has high resistance to passing through the intestine, prevents pathogenic insults and promotes the maturation of the immune system, it has been identified as a potential probiotic. L. fermentum has been shown to interact with human immune cells and to modulate specific pathways involved in innate and adaptive immune processes in diverse inflammatory diseases. This review summarizes the immunomodulatory properties and regulatory mechanisms of L. fermentum identified in isolated immune cells, animal models and the human body in recent studies.