- The objectives of this study were to compare antioxidant activity and the polyphenolic contents as well as effects of two types of pineapple extracts, Pattavia (Sriracha) and Nanglae, on CYP1A2, CYP2E1 and CYP2D6 activity using human liver microsomes and mechanisms involved. Cytotoxicity of pineapple extracts toward HepG2 cells was also evaluated. The results of this study show that Pattavia gained higher yield and higher total phenolic and flavonoid content compared to those of Nanglae (10.3 % vs 5.7% yield). By HPLC analysis, polyphenols containing in pineapple extracts both Pattavia and Nanglae were gallic acid, epigallocatechin and rutin. The content of these three compounds found in Pattavia was higher than those of Nanglae . Pattavia tend to be a more potent antioxidant than Nanglae according to IC50 derived from DPPH assay, superoxide radical and hydrogen peroxide scavenging assay. IC50 value of Pattavia were 65.18 μg/ml, 2.48 μg/ml and 106.75 μg/ml compared to those of Nanglae (116.65 μg/ml, 5.15 μg/ml and 109.10 μg/ml) in DPPH , superoxide and hydrogen peroxide assay, respectively. Both Pattavia and Nanglae extracts inhibited CYP1A2-, CYP2E1- and CYP2D6-mediated metabolisms . Pattavia and Nanglae exhibited similar extent of inhibition on CYP1A2 activity ( IC50 values of 266.87 μg/ml and 274.98 μg/ml, respectively), and on CYP2E1 activity with IC50 values of 152.41 μg/ml and 177.13 μg/ml, respectively, whereas Nanglae was more potent than Pattavia in inhibition of CYP2D6-mediated metabolism with IC50 values of 132.46 μg/ml and 445.04 μg/ml, respectively. Type of inhibition of pineapple extracts on the CYP-mediate metabolisms studied varied with competitive type for CYP1A2, noncompetitive type for CYP2E1 and uncompetitive type for CYP2D6. Effect of pineapple extracts on cancer cell, Hep G2, was investigated using MTT assay. Both Pattavia and Nanglae extracts showed cytotoxic effect with IC50 value of 22.40 μg/ml and 24.28 μg/ml, , respectively. The results of this study show that pineapple extracts, Pattavia and Nanglae, have chemopreventive potential in initiation, promotion and proliferation stage of carcinogenesis via inhibitory effects on bioactivation-related CYPs, antioxidant activity as well as cytotoxicity. Further studies need to be carried out to provide support for the use of pineapple extracts in chemoprevention.