Prior to consumption, African pumpkin leaves (Momordica balsamina L.) are generally cooked. In this study, the effects of common household cooking methods (boiling, steaming, microwaving, stir-frying) on bioactive metabolites, carotenoids, antioxidant activity, antinutrients and inhibitory effects on α-glucosidase and α-amylase activities were examined. A set of 14 bioactive metabolites were identified in raw and cooked African leaves using UPLC-QTOF/MS. The results showed that the four different types of household cooking methods had different effects on the bioactive metabolomics profile of African pumpkin leaves. In comparison to raw leaves and leaves cooked in other methods, the concentrations of six phenolic compounds, rutin, cryptochlorogenic acid (4-caffeoylquinic acid), pseudolaroside A, isorhamnetin 3-O-robinoside, quercetin 3-galactoside, and trans-4-feruloylquinic acid, were highest in stir-fried leaves. Of all household cooking methods tested, stir-frying increased the content of lutein, β-carotene, and zeaxanthin by 60.00%, 146.15%, and 123.51%, respectively. Moreover, stir-frying African pumpkin leaves increased the antioxidant activity (DPPH and ABTS) and the inhibition of α-glucosidase and α-amylase. Compared to all four methods of household cooking, stir-frying reduced the antinutritive compounds compared to raw leaves. This work provides useful information to the consumers on the selection of suitable cooking methods for African pumpkin leaves.