|Supramolecular chemistry deals with the study of organized molecular systems in which the molecules or ions are held together by non-covalent interactions [1, 2, 3]. The reversibility of such interactions makes supramolecular “dynamic” systems. This is the key principle on which the design of new molecular machines is based. Examples are given in Fig. 1-2.Also, the labile interactions between particular molecules and drug molecule are the way to develop new drug carriers which is nowadays topic of a high importance in medicine. The formation of supramolecular complexes is usually assisted by carrying out their synthesis preparing sufficient amount of the products and examining them by nuclear magnetic resonance (NMR) or other classical analytical techniques. This can be tedious and laborious process and might require rather high quantity of the reagents. Matrix Assisted Laser Desorption Ionisation (MALDI) and/or Surface Assisted Laser Desorption Ionisation (SALDI) Time Of Flight (TOF) mass spectrometry are traditionally used in Proteomics and Bio-Analytics. We have applied MALDI and SALDI for the fast screening to find out the formation of supramolecular complexes and/or to search for drug carriers. For this purpose, mass spectrometric analysis was used in combination with combinatorial experiments mixing the reactants, either in aqueous or organic phase and the products were then examined. Reactions can also be done directly on a MS target. In some cases, experimental design (ED) was also used in order to reduce the number of combinatorial experiments. In this work several examples of supramolecular complex formation using as hosts cyclic ethers, cyclodextrines, cucurbit[n]urils etc., and as guests fullerenes, nanoparticles, or drugs like antivirals, cisplatin, etc., will be given and discussed. The advantage is that the experiments can be done using minimal amount of the chemicals (such as 10-5 moles or less) which is important for scarce or expensive substances and materials. The proposed application of MALDI and SALDI TOF mass spectrometry with ED represents an efficient and economic way to search for the formation of new supramolecular complexes and/or for possible drug carriers.