A series of two-dimensional (2D) polyoxometalate-based frameworks, [Ln3(PDA)3(H2O)6(PMo12O40)]·xH2O (Ln = La (1); Ce (2); Pr (3); Nd (4); PDA = 1,10-phenanthroline-2,9-dicarboxylate), have been synthesized and structurally characterized by various analytical techniques. Single-crystal X-ray diffraction reveals that 1-4 have a unique 2D layer structure in which Keggin anions have coordinated upward and downward the plane, and this feature makes them suitable candidates for surface binding of common drugs via supramolecular and electrostatic interactions. Also, the ability of 1-4 (as the first polyoxomolybdate-containing frameworks) as sorbents for the extraction and quantitative determination of opioid drugs (morphine, methadone, and pethidine) was investigated by using dispersive micro-solid-phase extraction (D-μSPE) and high-performance liquid chromatography (HPLC). The method showed wide linear ranges in the range of 0.3 to 300 ng mg-1 and low limits of detection (LODs) ranged from 0.1 to 0.2 ng mg-1 of hair.