The deficient order in amorphous components severely affects the thermoelectric (TE) properties in polymers. Encouragingly, two-dimensional layered double hydroxides (LDHs) have been regarded as an efficient host material to tune the conformation of guest molecules and construct ordered hybrids. Herein, we report a facile construction of periodically ordered organic-inorganic TE hybrids by alternative stacking of inorganic LDH nanosheets and organic poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) (PEDOT:PSS) molecules. The ordered structure of PEDOT:PSS-LDH gave rise to the extended molecular configuration of PEDOT:PSS, resulting in the improved carrier mobility in the hybrids. Moreover, the energy filtering was induced by such a periodically ordered structure, which blocked the low-energy carriers preferentially and improved the Seebeck coefficient in the hybrids. Therefore, the power factor of the PEDOT:PSS-LDH hybrid was 120-fold higher than that of pristine PEDOT:PSS. These results not only establish an effective method for the construction of periodically ordered TE materials but also address the significance of an ordered structure of molecules in TE materials.