Natural products (phytochemicals), either as in whole food or as plant extracts,exhibit successful activity against numerous disease targets. Currently no efficient treatments are available that allow rapid and sustained decrease in blood ammonia levels. Natural plant phytochemicals have been reported to have some anti-hyperammonemic activity due to their antioxidant potential and removal of excess ammonia. This chapter reviews and discusses the medicinal properties and role of anti-hyperammonemic activity of natural plant phytochemicals such as Momordica charantia, Semecarpus anacardiumnut, Withania somnifera, Pongamia pinnata, Hibiscus sabdariffa, morin, and rutin. Natural products with antioxidant activity may be used to help in preventing a number of metabolic disorders and non-communicable diseases including hyperammonemia by reducing oxidative damage.