It is now widely appreciated that probiotics exert their beneficial effects through several mechanisms, including inhibitory effects on pathogens, maintenance of the balance of intestinal microbiota, and regulation of immune responses and intestinal epithelial homeostasis. A significant area of progress has come from observations that specific products derived from probiotics mediate their mechanism(s) of action. This review focuses on new insights into the well-studied probiotic bacterium GG (LGG). The biologic consequences of LGG-derived products enhance LGG adherence to intestinal epithelial cells and protect intestinal epithelial cells from injury through regulating several signaling pathways. Thus, LGG-derived products may provide novel approaches for health and disease prevention and treatment, especially for intestinal inflammatory disorders. However, compared to LGG functional proteins predicted by analysis of LGG genome sequences, the number of identified LGG-derived products is limited. As more mechanistic evidence becomes available to characterize the relationship between probiotics and host cellular responses, the development of more therapeutics from naturally derived or modified probiotics may be part of our future.