The present study used in vitro digestion coupled with Caco-2 cells to assess antioxidant and anti-inflammatory activities of an aqueous fraction from Albizia lebbeck (A. lebbeck) young leaves collected from 3 provinces of Thailand i.e.; Suphanburi (SP), Nakhonratchasima (NA) and Kanchanaburi (KA). A. lebbeck young leaves from SP had the highest content of flavonoids while those from KA possess the highest of carotenoids. The aqueous fraction of A. lebbeck young leaves from SP had the highest antioxidant capacity. Pre-treatment of Caco-2 cells monolayer with the aqueous fraction of A. lebbeck young leaves from SP significantly restored intracellular glutathione content and glutathione peroxidase activity induced by H2O2+IL-1β. Pre-incubation of Caco-2 cells monolayer with the aqueous fraction of A. lebbeck young leaves from 3 provinces significantly decreased secretion of IL-8 and MCP-1. Similar to the antioxidant capacity, the aqueous fraction of A. lebbeck young leaves from SP had the highest anti-inflammatory capacity. Pre-treatment of Caco-2 cells monolayer with the aqueous fraction of A. lebbeck young leaves from 3 provinces significantly decreased TNF-α and IL-6 production and COX-2 protein expression but there was no statistically difference noted in suppressive effect among samples from 3 provinces. The present data indicated that digested active compounds in A. lebbeck young leaves retained their antioxidant and anti-inflammatory capacity and enhanced cytoprotective effects by reducing potential damage caused by oxidative stress and inflammatory insult.