<p>Background: One of the important&nbsp;therapeutic approaches in cancer field is development of compounds which can block the initial tumor growth and the progression of tumor metastasis with no side effects. Thus, the recent study was carried out to design anti-VEGFR2-peptidomimetics as the most significant factor of angiogenesis process- and evaluate their biological activity by <em>in vitro</em> assays.</p> <p>Methods: We designed anti-VEGFR2 peptidomimetics with anti-angiogenic activity, including compound P (lactam derivative) and compound T (indole derivative) by using in silico methods. Then, the inhibitory activity on angiogenesis was evaluated by using angiogenesis specific assays such as Human Umbilical Vein Endothelial Cell (HUVEC) proliferation, tube formation in Matrigel, MTT and Real-Time PCR. IC50 values of the compounds were also determined by cytotoxicity plot in MTT assay.</p> <p>Results: Compounds P and T inhibited HUVEC cell proliferation and viability in a dose-dependent manner. The IC50 for compound T and compound P in HUVEC cell line were 113 and 115 <em>&mu;g/ml</em>, respectively. Tube formation assay revealed that both compounds can inhibit angiogenesis effectively. The results of Real-Time PCR also showed these compounds are able to inhibit the expression of <em>CD31</em> gene in HUVEC cell line.</p> <p>Conclusion: Our study suggested that compounds P and T may act as therapeutic molecules, or lead compounds for development of angiogenesis inhibitors in VEGF-related diseases.</p>