Since the early days of dendrimer chemistry, mass spectrometry has been an important analytical method for determining the purity and the detection of defects in dendrimers. Meanwhile, growing evidence demonstrates the great potential of mass spectrometry for the investigation of non-covalent dendritic host–guest complexes. Mass spectrometry provides an efficient means to isolate them in the high vacuum inside a mass spectrometer under environment-free conditions. Gas-phase chemistry is particularly beneficial for exploring the intrinsic properties which cannot easily be studied in solution. This mini-review highlights the versatility of gas-phase chemistry for (1) screening the specificity and stability of multivalent dendritic host–guest complexes depending on the nature of the guests, (2) revealing a dendritic effect during dendrimer–tweezer complex fragmentation and (3) monitoring an intra complex movement of small guests along the dendrimer periphery.