In this study, mesoporous silicate was applied as a matrix for the analysis of various molecules from small molecules to medium sized peptides in laser desorption/ionization mass spectrometry. In contrast with conventional matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS), the proposed approach, desorption/ionization on mesoporous silicate mass spectrometry (DIOM-MS), significantly reduces the problem of matrix interference in low mass region and can be applied to the analysis of versatile chemicals including amino acids, synthetic drugs, peptides and others. In addition, distinctive advantage of DIOM-MS showed higher salt tolerance and could be applied to identify the proteins from the analysis of tryptically digested peptides. DIOM-MS has several availabilities such as easy sample preparation, rapid analysis of small molecules without noise, peptide analysis without organic matrix, high salt tolerance, versatile coupling with other separation techniques, and high throughput manner.