Milk thistle, Silybum marianum, is a medicinal plant grown for its bioactive compounds with well-documented antioxidant and hepatoprotective properties. Milk thistle has a well-established pharmacological reputation for treatments of human liver disease, but it is also used in animals. This review summarizes the experimental evidence of milk thistle’s effects on animals when administered as silymarin extract (feed additive) or a feed ingredient, if administered as seed or expeller/cake with the seed residue still containing the bioactive components. The use as a feed additive or feed ingredient is motivated by the complexity of silymarin registration as a veterinary drug. In farm animals the drug improves the animals’ performance and product quality and oxidative stability, supports liver function during productive life-cycle, improves gut-health and morphology, and can reduce intestinal pathogens. In dogs and cats the treatment is focused on acute and chronic liver diseases including the detoxification processes and support of drug treatments including chemotherapy. In equine athletes milk seed cake showed positive effects and a faster return of cortisol to the resting values before exercise occurred. In aquaculture it confirms its usefulness in supporting animal health and performance. In certain studies it is not clear what has been administered, and the composition and doses are not always clearly reported. A few studies reported no effects, but none reported problems connected to milk thistle administration. However, the overall picture shows that the use of milk thistle results in improved or restored health parameters or better animal performance.