The seeds of dissected hogweed (Heracleum dissectumLedeb., Apiaceae) are the source of hogweed oil (HSO), which is still underexplored and requires careful chemical and biological studies. The performed physico–chemical analysis of HSO elucidated basic physical characteristics and revealed the presence of fatty acids, essential oil components, pigments, and coumarins. High-performance liquid chromatography with photodiode array detection and electrospray ionization triple quadrupole mass spectrometric detection (HPLC–PDA–ESI–tQ–MS/MS) identified 38 coumarins that were characterized and quantified. Various furanocoumarins were the major components of HSO polyphenolics, including imperatorin, phellopterin, and isoimperatorin, and the total coumarin content in HSO varied from 181.14 to 238.42 mg/mL. The analysis of storage stability of the selected compounds in HSO indicated their good preservation after 3-year storage at cold and freezing temperatures. The application of the CO2-assisted effervescence method allowed the production of an HSO nanosuspension, which was used in a brain ischemia model of rats. The HSO nanosuspension enhanced cerebral hemodynamics and decreased the frequency of necrotic processes in the brain tissue. Thus,H. dissectumseeds are a good source of coumarins, and HSO nanosuspension promotes neuroprotection of the brain after lesions, which supports earlier ethnopharmacological data.