The current study aimed to investigate the phytochemical profile and the in vitro estrogenic activity of Phoenix rupicola T. Anderson seeds' extracts. Gas chromatography/ mass spectrometry (GC/MS) of the petroleum ether (seed oil) and chloroform extracts revealed the characterization of 93 compounds. γ-Sitosterol (8.54%), n-dodecane (6.00%), n-undecane (5.87%) and (2E)-2-decenal (3.48%) represented the major compounds in the petroleum ether extract, whereas lauric acid (21.73%), γ-sitosterol (21.21%), palmitic acid (9.19%) and myristic acid (6.37%) were the main components in the chloroform extract. Moreover, investigation of the 70% aqueous methanol extract by high-performance liquid chromatography coupled with diode-array detector (HPLC-DAD) revealed the identification of 13 phenolic compounds, of which catechin (105.75 mg%), vanillic acid (58.26%), p-hydroxybenzoic acid (32.84%) and cinnamic acid (27.62%) dominated The estrogenic activity of the extracts was tested in vitro via sulforhodamine B (SRB) assay on MCF-7 cells, where petroleum ether extract at a dose of 10 ug/mL exhibited the highest activity (p < 0.05) indicated by 1.17 % increase in cells' proliferation compared to 17β-estradiol. Consequently, P. rupicola seeds provide a promising source of phytoconstituents with estrogenic activity worthy for further detailed studies.