Microwave-induced plasma (MIP) with different discharge gases of argon or helium provides significant plasma-based ambient desorption/ionization sources, which have potential applicability in direct analysis of complex samples without any sample pre-treatment. In this study, experiments were conducted to better understand microwave-induced plasma desorption/ionization (MIPDI) sources and the corresponding ionization mechanisms. Emission spectra of microwave-induced argon (MIP-Ar) and helium (MIP-He) plasmas were obtained from the plasma tail flame of a MIP source. Compounds including L-phenylalanine, L-serine, L-valine, urea, 4-acetaminophen, gallic acid and L-ascorbic acid were analyzed using both sources. Polyethylene glycol 400 (PEG400) oligomers were detected by MIP-Ar and MIP-He mass spectrometry at different microwave powers. Mass spectra of higher molecular weight PEGs (including PEG800, PEG1000 and PEG2000) were also acquired using both sources. In the emission spectra, N2 , H-I and O-I species were observed by MIP-Ar/He. In addition, SiO2 , Na-I, Si-I and Si-II species were generated by MIP-He. In the mass spectra of compounds, [M+H]+ , [2M+H]+ , [M+O+H]+ , [M+2O-H]+ and fragment ions were observed. In the mass spectra of PEG400 obtained by MIP-Ar/He at different microwave powers, higher molecular weight oligomers could only be observed with higher microwave power. PEGs with molecular weights as high as 1000Da were also successfully analyzed by MIPDI. According to the different natures of the samples, either MIP-Ar or MIP-He can be chosen as a working ion source for mass spectrometry. The MIPDI source is potentially applicable to the analysis of compounds with high molecular weights, especially polymers with high degree of polymerization (such as PEG2000), which is a challenging issue for the traditional ambient ionization sources. Copyright © 2017 John Wiley & Sons, Ltd.