Four new inorganic–organic hybrid polyoxomolybdates K2[SeIVMo6O21(L-O2CCHNH3 CH2OH)3]·6H2O (1) and K2[SeIVMo6O21(D-O2CCHNH3CH2OH)3]·6H2O (2), K2[TeIVMo6O21(D-O2 CCHNH3CH2OH)3]·6H2O (3) and K2[TeIVMo6O21(L-O2CCHNH3CH2OH)3]·6H2O (4) have been synthesized by a simple one-pot reaction of NaMoO4·2H2O, Na2SeO3/K2TeO3, KCl and corresponding chiral serine ligands in the aqueous medium and further characterized by single-crystal X-ray diffraction, elemental analyses, IR spectra, thermogravimetric (TG) analyses, electrospray ionization mass spectrometry (ESI-MS) and circular dichroism (CD) spectra. 1–4 are the representative chiral heteropolymolybdates featuring that a common {Se/TeMo6} fragment is made up of a six-membered MoO6 octahedral ring functionalized by three serine ligands. TG analyses reveal that 1–4 undergo a two-step weight loss in the temperature range of 25–850°C.