Silybin is the main component of silymarin and is a polyphenolic bioactive natural product found in the milk thistle plant Silybum marianum. Silybin possesses many health-promoting benefits, such as antioxidation and anticancer. However, the benefits are curtailed by its extremely poor water solubility. Consequently, the bioavailability and therapeutic effective of silybin is also limited. Nanotechnology is an available approach to solving these issues. Currently, nanosuspensions, micelles, nanoparticles, nano-emulsions, etc. are used to improve the in vitro dissolution velocity and in vivo efficiency of silybin. The present work reviews the nanotechnology-based applications and developments on silybin production. Silybin can also be utilized as a reference for the production and development of other water-insoluble drug delivery systems.