To elucidate the structural requirements by which EGCG analogs inhibit Aβ42 protein aggregation and remodel amyloid fibers, the molecular interactions between Aβ42 and four EGCG analogs, epigallocatechin-3-gallate (EGCG), (−)-gallocatechin gallate (GCG), (−)-epicatechin-3-gallate (ECG) and (−)-epigallocatechin (EGC), were investigated by thioflavin T fluorescence (ThT), circular dichroism (CD), atomic force microscopy (AFM), differential scanning calorimetry (DSC) and BCA protein assay. Results revealed that the four EGCG analogs had the ability to prevent the increase of β-sheet content and inhibit Aβ42 fibrillation when added in the lag and growth phases of Aβ42 fibrillation process. When added in the equilibrium phase, the four EGCG analogs can disaggregate the preformed protofibrils/fibrils to oligomers and unfold or partially unfold oligomers. It was also observed that EGCG showed the highest inhibitory effect on Aβ42 fibrillation, followed by GCG, ECG and EGC. From the values of IC₅₀, kinetic parameters, secondary structures, thermo-stability and solubility measurement, a reasonable conclusion can be preliminarily drawn that the structural contribution efficiency of EGCG to inhibit Aβ42 aggregation and remodel Aβ42 amyloid fibrils decreases by the order of 3′-hydroxyl group of trihydroxyphenyl ring > gallol ester moiety > stereoisomer. The findings in this work provide the structure based molecular interaction mechanism between EGCG analogs and Aβ42 amyloid protein.