Polyphenol from fruits and vegetables have been proved that can lower the risk of many chronic disease. However, most studies are only focus on the extractable polyphenols right now. Non-extractable polyphenols may also have many important biological effects. The objective of this study was to find the difference between the extractable polyphenol and non-extractable by alkaline hydrolysis, acid hydrolysis and enzyme hydrolysis, compare the total phenolic content, flavonoid content and tannin content, and study their anti-inflammation effect, anti-cancer effect and antioxidant effect. The results showed that NEP alkaline hydrolysis was the best way to extract mango polyphenol. It had the highest total phenolic content and tannin content. The ORAC data also showed NEP alkaline hydrolysis had the best antioxidant effect. NEP alkaline also showed the dose-dependent inhibition manner. The extractable polyphenol showed better anti-inflammation effect then non-extractable polyphenol. Overall, we can conclude the secondary extraction did in fact yield more polyphenol from residue and non-extractable polyphenol have very similar effects as the extractable polyphenol.