In this study, 18 natural products were screened via anti-angiogenesis experiments, and 1 candidate product was identified, Siegesbeckiae herba, which exerted dose-dependent inhibitory effects against angiogenesis, adipogenesis, and cell adhesion. S. herba extract (SHE) exhibits an angiogenesis inhibitory effect superior to that of the EGCG from green tea leaves. The expression level of angiogenesis and adipogenesis-related signal molecules in the western blotting was reduced by increasing the amount of added SHE. Moreover, a diet supplemented with SHE was deemed more effective in inducing weight loss in LB mice than a representative synthetic diet drug, orlistat, which incidently caused the side effect of denuding the mice of their hair. These results indicate that S. herba may prove to be a useful anti-adipogenic compound, and these in vitro results may be reflected later under in vivo conditions.