The phytochemical analysis of Staehelina fruticosa led to the isolation of four germacranolide-type sesquiterpene lactones (1- 4), including two new glycosides. The structures of these sesquiterpene lactones were elucidated using spectroscopic techniques, and enzymatic hydrolysis was carried out to confirm the nature of the two glycoside derivatives. Molecular modeling was incorporated to substantiate their relative configuration.