The effect of trehalose on the aggregation of β-amyloid (Aβ) was investigated using quartz crystal microbalance (QCM) and circular dichroism spectroscopy (CD). Here we prepared three types of host Aβ-guest Aβ systems differing in a combination of their secondary structures: namely, β-sheet-β-sheet (system (1)), β-sheet-random coil (system(2)) and random coil-random coil (system(3)). The host Aβ was fixed on the electrode of QCM, and the guest Aβ was dissolved in a buffer solution. The host-guest interaction was monitored through a frequency shift (ΔF) of the quartz vibration: a larger ΔF value means the occurrence of a larger degree of host-guest aggregation. When disaccharide (trehalose, neotrehalose or maltose) was added in the above system, the time dependent profile of ΔF was significantly affected. In systems (1) and (2), any of these disaccharides depressed significantly the host-guest aggregation: maltose and trehalose exhibited the strongest effect in systems (1) and (2), respectively. Interestingly, in system(3), trehalose rather promoted the aggregation compared with the control (without disaccharide), while both maltose and neotrehalose depressed the aggregation as much as in the cases of systems (1) and (2). The results of systems (2) and (3) imply that trehalose more strongly interacts with Aβ in a random coil than that in p-sheets. In fact, CD measurements indicated that trehalose retarded the transformation of Aβ from a random coil to β-sheet. Taken together, these results open up the possibility that trehalose modifies the aggregation process of Aβ through its preferential interaction with the random coil state of Aβ.