High intake of plant foods is associated with lower risk of chronic diseases as suggested by epidemiological evidence. This study aimed to investigate the anti-inflammatory potential of polyphenol rich fraction of Ipomoea batatas leaf extract and the compounds possibly responsible for the activity using LCMS. The anti-inflammatory studies were carried out in vitro by protein denaturation technique. The result shows significant different (p<0.05) percentage inhibition of denaturation 90.59% at 1000 μg/ml of the extract compared to the standard drug (declofenac) 95.12% at 1000 μg/ml. The LCMS profiling of the extract revealed the presence of many metabolites (polyphenols) such as chrogenic acid, myricetin, furocoumarinic acid, aromadendrin, naringenin, 4,5-dicaffeolquinic acid and abietinol among others. The presence of these metabolites could be the reason for the anti-inflammatory effect of the extract observed. This implies that the plant can be exploited for its medicinal, therapeutic properties and possibly used to reduce the risk of many chronic diseases. Keyword: Anti-inflammatory activity, Protein denaturation technique, Mother delight, LCMS, Phytochemicals.