Autophagy is a ubiquitous mechanism for maintaining cellular homeostasis through the degradation of long-lived proteins, insoluble protein aggregates, and superfluous or damaged organelles. Dysfunctional autophagy is observed in a variety of human diseases. With advanced research into the role that autophagy plays in physiological and pathological conditions, targeting autophagy is becoming a novel tactic for disease management. Saponins are naturally occurring glycosides containing triterpenoids or steroidal sapogenins as aglycones, and some saponins are reported to modulate autophagy. Research suggests that saponins may have therapeutic and preventive efficacy against many autophagy-related diseases. Therefore, this review comprehensively summarizes and discusses the reported saponins that exhibit autophagy regulating activities. In addition, the relevant signaling pathways that the mechanisms involved in regulating autophagy and the targeted diseases were also discussed. By regulating autophagy and related pathways, saponins exhibit bioactivities against cancer, neurodegenerative diseases, atherosclerosis and other cardiac diseases, kidney diseases, liver diseases, acute pancreatitis, and osteoporosis. This review provides an overview of the autophagy-regulating activity of saponins, the underlying mechanisms and potential applications for managing various diseases.