Introduction: Active natural products from medicinal plants are good sources for the antioxidant and antidiabetic agent. Natural antioxidants protect human health against oxidative stress and free radicals which cause degenerative disease such as diabetes. Objectives: This study was conduct to try one approach to treat diabetes that is to reduce gastrointestinal glucose absorption through the inhibition of the α-glucosidase enzyme. Methods: We make three different root extracts from Durio zibethinus Murr. The extracts were examined for their DPPH radical scavenging activity, antioxidant activity using β-carotene-linoleic acid assay, and their α-glucosidase inhibitory activity by a standard method. Additionally, we have also determined their total polyphenols and total flavonoids quantitatively using spectrophotometer UV-Vis. Results: The root extracts Durio zibethinus Murr. were effectively scavenged DPPH radicals in varied rate. The hexane (EHD), ethyl acetate (EEAD), and ethanol (EED) extracts revealed DPPH radical scavenging activity with IC50 of 541.28, 83.95 and 11.24 μg/ml respectively and their β-carotene-linoleic acid assay showed activity with IC50 of 273.58, 139.53, and 166.83 μg/ml, respectively. In vitro assay of the α-glucosidase inhibitory activity of the EHD, EEAD, and EED extracts showed an IC50 of 119.84, 23.69, and 3.35 μg/ml, respectively. Conclution: In this present study, we found that ethanol extract revealed the most active antioxidant activity and the highest inhibitory activity against α-glucosidase enzyme. The total phenolics and total flavonoids contents of the extracts were studied, where the ethanol extracts were found to have the highest than that of other extracts. This study proofs the medicinal potencies of Durio zibethinus Murr. root extracts.