Various functionalized mono- and diarylanthranilo-1,3-dinitriles were synthesized and evaluated for their in vitro antihyperglycemic activity against the PTP-1B, glucose-6-phosphatase, glycogen phosphorylase and alpha-glucosidase enzymes. Among various screened compounds, 5,6-diaryl substituted anthranilo-1,3-dinitriles 3a, 3b, and 3d showed good inhibitory activity against PTP-1B with IC(50) values of 58-72 microM. Three of the test compounds showed significant (25-37%) lowering of plasma glucose level at 24h in sucrose-challenged streptozotocin-induced diabetic Sprague-Dawley rat model.