Ginsenoside Rg5 plays a novel role as an IGF-1R agonist. Ginsenoside Rg5 binds to IGF-1R with an IC50 value of ~90 and its angiogenic activity is inhibited by IGF-1R knockdown. To investigate the possible interaction of Ginsenoside Rg5 with IGF-1R, a docking analysis is performed. Docking results show that Ginsenoside Rg5 binds strongly at two sites, A and B, with Kd values of 20 and 27 nM, respectively, to the cysteine-rich domain of IGF-1R. Pretreatment with Rg5 blocks the binding of radiolabeled IGF-1 to HUVECs with an IC50 value of ~90 μM, which is greater than an IC50 value of ~1.4 nM for unlabeled IGF-1. The results from MTT assay show that MCF-7 cell proliferation is inhibited by Ginsenoside Rg5 treatment for 24, 48 and 72 h in a dose-dependent manner. Ginsenoside Rg5 at different concentrations (0, 25, 50 and 100 μM), induce cell cycle arrest in G0/G1 phase through regulation of cell cycle-related proteins in MCF-7 cells.