Abstract The antioxidant activity of acetone extracts and purified fractions from Prosopis laevigata leaves were evaluated as well its cardioprotection potential in vitro. Mezquite leaves were dewaxed with petroleum ether and extracted with aqueous acetone (70%); the polar extract was purified in Sep-Pak® Cartridges and their fractions evaluated. Significant differences among fractions and crude extracts were found in total phenolic content (Folin Ciocalteu), antioxidant capacity by scavenging hydroxyl and DPPH radical assays. Purified fractions showed antihypertensive effects inhibiting angiotensin converting enzyme and cardioprotection inhibiting low density lipoprotein oxidation. The HPLC profile displayed phenolic compounds such as gallic acid, catechin, gallocatechin, epicatechin gallate, rutin, and luteolin that may explain these antioxidant and biological properties. Mesquite leaves can be a source of bioactive phenolics as nutraceutical ingredients.