In the present study, the purification and extraction of five chemical warfare agent (CWA) simulants, dimethyl methyl phosphonate, di(propylene glycol) methyl ether, methyl salicylate, triethyl phosphate, and diethyl phthalate, on a digital microfluidic (DMF) device were demonstrated. The DMF on-chip purification and extraction was performed using a magnetic bead (MB)-based diol solid-phase extraction procedure. The extracted CWA simulants were detected using both matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and gas chromatography-mass spectrometry (GC-MS). The method detection limits of the DMF-MS approach using diol-MBs were also determined. In particular, for the DMF-GC-MS, the quantitative analysis ability was validated by determining accuracy, precision, calibration curve performance, and recovery efficiency. This study clearly shows that the CWA analyses can be automated on the DMF-MS platform, thereby minimizing human involvement.