Five new compounds, three iridoid glycosides (1-3) and two triterpenoid saponins (4, 5), along with thirty-two known compounds were isolated from the methanolic extract of the leaves of Dolichandrone spathacea. This traditional medicinal plant is widely used in Asia and India as antiseptic, for bronchitis and thrush treatment, and the methanolic extract has been shown to possess antibacterial activity against methicillin-resistant Staphylococcus aureus. The new iridoids were esterified derivatives of 6-ajugol and 6-catalpol, and the new saponins were glucosides of two polyhydroxy triterpenes with ursan skeleton. Their structures were elucidated by spectroscopic methods, including 1D and 2D NMR experiments and HR-ESI-MS analysis, and from comparison with the literature. This study aimed at investigating extracts and isolated compounds for their antimicrobial activities against bacterial and yeast strains, in order to validate the uses of the plant in folk medicine. The 6-O-esterified iridoids had weaker antibacterial activity; verbascoside and p-methoxycinnamic acid, the major compounds of the methanol extract, possessed strong antibacterial activity, which could account for the traditional antiseptic and anti-infectious uses of the leaves of D. spathacea.