Type 2 diabetes mellitus is a serious global health problem that has increased dramatically in incidence in recent decades due to excessive food intake and an increased sedentary lifestyle. While a small number of drugs have been developed to treat the condition, new agents and therapies are urgently needed for suitable treatment. Acacia spp. are renowned for their traditional uses in the treatment of many ailments including diabetes, and evidence has emerged demonstrating the capabilities of the plant to treat high blood sugar. Extracts and phytochemicals derived from all parts of Acacia plants have been found to lower plasma glucose, highlighting the potential of this plant as a source of novel anti-diabetic medicines. This is discussed in this chapter, in addition to the evidence for the enzymes and phytochemicals present in Acacia spp. that may be responsible for the decreases in blood glucose and the mechanisms of action of these agents, including their effects on inflammation pathways.