Here, we report crude extract screening of 40 Vietnamese plant extracts (from 18 different plant species used for the treatment of type 2 diabetes) for PTP1B inhibitors, followed by high-resolution PTP1B inhibition profiling in combination with HPLC-HRMS-SPE-NMR analysis for identification of bioactive constituents. The gene discussed is PTPN1; the disease is type 2 diabetes mellitus.