The mango is a rich source of various polyphenolic compounds. The major polyphenols in the mango in terms of antioxidative capacity and/or quantity are: mangiferin, catechins, quercetin, kaempferol, rhamnetin, anthocyanins, gallic and ellagic acids, propyl and methyl gallate, benzoic acid, and protocatechuic acid. The nutraceutical and pharmaceutical significance of mangiferin, which is a special polyphenol in the mango has been extensively demonstrated and continues to attract much attention especially in its potential to combat degenerative diseases like heart diseases and cancer. The amounts of the different polyphenolic compounds in the mango vary from part to part (pulp, peel, seed, bark, leaf, and flower) with most polyphenols being found in all the parts. Mango polyphenols, like other polyphenolic compounds, work mainly as antioxidants, a property that enables them to protect human cells against damage due to oxidative stress leading to lipid peroxidation, DNA damage, and many degenerative diseases. Use of pure isolated compounds has been found to be less effective than the use of crude mixtures from the particular mango part suggesting that synergism of the various mango polyphenols is important for maximum antioxidative activity. In this article, we review the major mango polyphenols, looking at their proposed antioxidative activity, estimated amounts in the different parts, their structures, suggested modes of action, and related significance to human health, with great emphasis on mangiferin.