Velvet antler is the only renewable bone tissue of mammalian animals, which consists of a variety of growth factors, amino acids and polypeptides. But the mechanism of high-speed proliferation without carcinogenesis is still mystifying. The previous study of this work found that the velvet antler peptides (VAP) could not only inhibit the proliferation and migration of osteosarcoma cell lines MG-63 and U2OS, but also induced U2OS apoptosis and inhibited MG-63 epithelial-mesenchymal transition (EMT) through TGF-β and Notch pathways. These results lead us to conclude that VAP has the potential ability to mediate osteosarcoma cells by regulating related signaling pathways and growth factors. Therefore, finding a new appropriate inhibitor for OS is a valuable research direction, which will give patients a better chance to receive proper therapy. From an applied perspective, this review summarized the effects of velvet antler, genes, growth factors and research progress of relative pathways and genes of osteosarcoma, which are poised to help link regenerative molecular biology and regenerative medicine in osteosarcoma pathogenesis.