Type-2 diabetes is affecting 246 million people worldwide [1]. Patients with type-2 diabetes suffer from complications such as high blood pressure, blindness, kidney failure, lower limb amputation, heart disease and stroke. In this study, 18 medicinal plants traditionally used in Vietnam for treatment of diabetes were investigated for inhibition of human recombinant protein-tyrosine phosphatase 1B enzyme (PTP1B) based on a recently developed microplate-based assay [2]. This enzyme is a key negative regulator of the insulin signaling pathway and is considered a promising potential therapeutic target, in particular for treatment of type-2 diabetes. Ethyl acetate extracts of Rhizophora mucronata, Kandelia candel, Nepenthes mirabilis, Phyllanthus amarus, Phyllanthus urinaria, Ludwigia octavalvis, Euphorbia hirta, Syzygium cumini, Ficus racemosa, Pithecellobium ducle, Cassia fistula, and Pandanus odoratissimus as well as butanol extracts of R. mucronata, K. candel, N. mirabilis, P. urinaria, L. octavalvis, Lagerstroemia speciosa, E. hirta, F. racemosa, and P. odoratissimus inhibited PTP1B more than 80% at concentrations of 100 µg/mL. All active extracts were subsequently subjected to analytical-scale HPLC, and this showed that ethyl acetate and butanol extracts of R. mucronata and K. candel contained high levels of tannins, and were therefore not investigated further. Ethyl acetate extracts of N. mirabilis, P. amarus, P. urinaria, L. octavalvis, E. hirta, S. cumini, F. racemosa, P. ducle, C. fistula, and P. odoratissimus showed IC50 values of 1.4 ± 0.05, 14.0 ± 0.8, 74.4 ± 3.9, 16.9 ± 3.2, 29.2 ± 6.2, 27.5 ± 7.8, 38.3 ± 10.6, 26.1 ± 2.5, 24.1 ± 8.4, and 20.8 ± 5.6 µg/mL, respectively. Meanwhile, butanol extracts of N. mirabilis, P. urinaria, L. octavalvis, L. speciosa, E. hirta, F. racemosa, and P. odoratissimus showed IC50 values of 0.4 ± 0.1, 10.8 ± 0.9, 3.3 ± 0.3, 19.6 ± 5.1, 38.2 ± 1.9, 3.6 ± 1.4, and 40.4 ± 7.9 µg/mL, respectively.