Diosgenin is a steroidal sapogenin compound in several plants such as Dioscorea spp., fenugreek, Polygonatum spp., and Smilax spp. The rhizomes of Dioscorea batatas (Chinese yam) and Dioscorea japonica (Japanese yam) are known informally in Japanese as "nagaimo" and "yamanoimo", respectively, and are also listed in the Japanese Pharmacopoeia as the crude drug "sanyaku". Diosgenin has clear effects on a diverse range of diseases. Among them, improvement of cognitive function by diosgenin has been substantially studied. Administration of diosgenin to Alzheimer's disease model mice restored memory impairment. The receptor of diosgenin in neurons was identified as 1,25D3-membrane-associated rapid-response steroid binding protein (1,25D3-MARRS). By visualization of axon-growing neurons, the molecules responsible for axonal repairing were found to be SPARC and Galectin-1. Increases in SPARC and Galectin-1 were mediated by 1,25D3-MARRS stimulation. Diosgenin-high content Chinese yam extract was evaluated in humans for its effect on cognitive performance. The randomized, double blinded, crossover clinical study demonstrated upregulation of cognitive function by taking yam extract for 12 weeks. Interestingly, diosgenin has a variety of ameliorative effects on other diseases, such as cancer, obesity, non-alcoholic fatty liver disease, decreased bone density, hypertension, depression, ischemia, multiple sclerosis, diabetic peripheral neuropathy, and spinal cord injury, which are outlined in this review.