The self-assembly of the amyloid-β (Aβ) peptide of various amino acid lengths into senile plaques is one hallmark of Alzheimer’s disease pathology. In the past decade, many small molecules, including NQTrp, have been identified to reduce aggregation and toxicity. However, due to the heterogeneity of the conformational ensemble of Aβ with drugs, we lack detailed structures of the transient complexes. Following our previous simulation of the monomer of Aβ1-28, here we characterize the equilibrium ensemble of the Aβ1-28 monomer with NQTrp by means of extensive atomistic replica exchange molecular dynamics simulations using a force field to fold diverse proteins correctly. While the secondary structure content and the intrinsic disorder of the whole peptides are very similar and the lifetimes of the salt-bridges remain constant, the population of β-hairpin is reduced by a factor of 1.5 and the population of α-helix in the region 17-24 is increased by a factor of two upon NQTrp binding. These two factors, which impact the free energy barrier for nucleation, provide a first explanation for the reported reduced Aβ1-40/1-42 aggregation kinetics in the presence of NQTrp. Backbone and side-chain interactions of Aβ with NQTrp may also inhibit Aβ-Aβ contacts. The fraction of free Aβ1-28 monomer is, however, on the order of 20-25% at 17.5 mM, and this shows that the affinity of NQTrp is low and hence its inhibitory activity is not very strong. This inhibitor can be improved to reduce the formation of dimer, a critical step in aggregation and toxicity.