The study aims to investigate the effective components of Semen Ziziphi Spinosae (SZR) in nourishing the heart and tranquilizing the mind. A method of ultra high liquid chromatography (UHPLC) coupled with Q Exactive high resolution mass spectrometry (HR-MS) was developed. Based on the UV spectra, retention time and MS spectra, 25 compounds of SZR extract were identified or tentatively characterized, including 12 flavonoids, 8 triterpenoids saponins, 2 fatty acid and 3 alakoids. The study illuminated the major chemical components. Twenty bioactive components were determined in rat urine after oral administration of SZR extract by “in vitro to in vivo” translation approach, including 16 prototype compounds and 4 metabolites. Spinosin, swertisin, jujuboside A and B were considered as the effective and active constituents in SZR of the sedative and hypnotic effects, which emodies characteristics of multiple components. It was beneficial exploration for searching the effective and active constituents of SZR in nourishing the heart and tranquilizing the mind.