The activation of vascular endothelial growth factor receptor-1 (VEGFR-1, also known as Flt-1) is crucial in many physiological and pathological conditions, like angiogenesis, cancer, inflammation, hematopoiesis, bone marrow precursors/stem cells recruitment in tumor angiogenesis, and metastasis formation. Many recent reports indicate that molecules able to antagonize Flt-1 activity have gained a strong interest in the view of therapeutic approaches. In order to identify new compounds able to interfere in the Flt-1 recognition by VEGFs family members, we have developed a highly sensitive competitive ELISA-based screening to study plant extracts and derivatives. Several fractions of the N-butanol extract of Pteleopsis suberosa leaves and of the chloroform extract of Parinari campestris leaves demonstrated by a bioassay-guided fractionation an evident inhibition of VEGF-A or placental growth factor (PlGF) interaction with Flt-1, with an inhibition over 50 % in particular for the VEGF-A/Flt-1 interaction at a concentration of 100 microg/mL. This activity seems be due to the presence of a combination of compounds acting synergistically.