<p>Laser-induced acoustic desorption (LIAD) coupled with dielectric barrier discharge ionization mass spectrometry (DBDI-MS) has been developed as a novel technique for the direct detection of solid samples. LIAD is a “soft” desorption method that enables the volatilization of thermally labile and involatile compounds without significant degradation, while DBDI provides a gentle ionization process. Compared with laser desorption DBDI-MS (LD-DBDI-MS) or laser desorption ionization-MS (LDI-MS), this combination allows for the analysis of fragile molecules with minimal fragmentation. In this study, we optimized the LIAD-DBDI-MS system by adjusting key parameters such as the distance between the titanium foil and the ion source inlet, and the laser power density. The system was successfully employed for the analysis of melamine, copper phthalocyanine, and folic acid, demonstrating its capability to detect molecular species primarily as intact [M + H]⁺ or [M]⁻ ions with minimal or no fragmentation. The results highlight the potential of LIAD-DBDI-MS as a powerful tool for the analysis of complexes and fragile compounds in various fields, including pharmaceuticals and materials science.</p> Graphical abstract <p></p>