From the bark of Guazuma ulmifolia, a plant used as anti-inflammatory remedy, the flavanocoumarin epiphyllocoumarin (1) along with epiphyllocoumarin-[4β→8]-(-)-epicatechin (2) and epiphyllocoumarin-[4β→8]-(-)-epicatechin-[4β→8]-(-)-epicatechin (3), never reported before, have been isolated. The structures of the proantocyanidins 2-3 have been elucidated by extensive NMR and ESI-MS analysis. On the basis of the flavane nature of the isolated compounds and considering the strong anti-STAT1 activity reported for epigallocatechin 3-O-gallate (EGCG), the affinity of compounds 1-3 for STAT1 has been evaluated by Surface Plasmon Resonance. Compounds 1-2 showed affinity for STAT1 comparable to that exerted by EGCG. In order to confirm this result, molecular docking studies to evaluate the interactions of compounds 1-3, phyllocoumarin (4), the reference compound EGCG (5), and its related compound (+)-gallocatechin 3-O-gallate (6) with STAT1 have been carried out. Furthermore the ability of compounds 1-3 to inhibit STAT1 activation has been evaluated using a nuclear extract obtained from the human monocytic leukemia cell line TPH-1. Flavanocoumarins 1-2 inhibited STAT1-DNA binding.