One flavonol glycoside, two O-isoprenylated flavonols, one α,α-dimethylallyl flavonol, one dihydrochalcone, two furanocoumarins and one terpenoid previously undescribed, along with 42 known compounds were isolated from the buds of two European Platanaceae, Platanus orientalis and Platanus × acerifolia. Their chemical structures were elucidated on the basis of spectroscopic analysis, including homonuclear and heteronuclear correlation NMR (COSY, NOESY, HSQC, and HMBC) experiments, as well as HRMS data. The estrogen-like and antiestrogen-like activity of dichloromethane and methanol extracts of P. orientalis and P. × acerifolia buds and isolated compounds was evaluated using estrogen-responsive cell lines. The potency of selected estrogen agonists to regulate gene expression through ERα and/or ERβ was compared with their in vitro osteoblastogenic activity. Kaempferol and 8-C-(1,1-dimethyl-2-propen-1-yl)-5,7-dihydroxyflavonol displayed osteoblastogenic as well as ERα-mediated estrogenic activity similar to estradiol.