Consumption of diets rich in phenolic compounds has been associated with reduced risk of chronic diseases. The effect of cooking and simulated gastrointestinal digestion on phenolic compounds and antioxidant properties of two cowpea (Vigna unguiculata) types was determined. Phenolic acids, flavan-3-ols and flavonols were the main groups of phenolic compounds identified. Cooking and simulated enzyme digestion of the cooked cowpea samples rendered some phenolics less extractable (possibly by promoting binding with other food components) or more extractable (possibly by release of bound forms). Total phenolic contents and radical scavenging properties of the cowpeas were reduced upon cooking, but increased upon simulated enzyme digestion. Cowpea extracts inhibited human LDL oxidation at a concentration of 2 mg mL−1 possibly due to their phenolic content. Phenolic compounds in cowpea can potentially protect against cardiovascular diseases for which LDL oxidation is a risk factor.