The comparative phytochemical analysis in this study revealed differences in the type and levels of phenolic compounds between Spiraea hypericifolia L. and Spiraea crenata L. The compounds in water–ethanol extracts of aerial parts of both species were identified by high-performance liquid chromatography as chlorogenic, gentisic, and cinnamic acids; quercetin; kaempferol; hyperoside; isoquercetin; nicotiflorin; and apigenin. In the extract of S. hypericifolia, p-coumaric acid and luteolin were also found, which were absent in the extract of S. crenata. Such compounds as avicularin, astragalin, and isorhamnetin-3-rutinoside proved to be specific to S. crenata (and were not found in the S. hypericifolia extract). The viability of liver cancer HepG2 cells and breast cancer MDA-MB-231 cells significantly decreased after cultivation with the S. crenata extract. In addition, the S. crenata extract showed higher antioxidant activity than the S. hypericifolia extract. It is most likely that these effects can be explained by the higher content of individual flavonoids in the extract of S. crenata. Thus, the extract of S. crenata holds promise for more extensive research on the mechanism of its action on tumor cells.