This paper presents the first effort to investigate the effects of uniform and nonuniform prestraining on the mechanical properties of nanostructured multilayers. Thin muscovite sheets were first subjected to a loading-unloading cycle under unidirectional compression and cantilever bending modes that induce uniform and nonuniform prestraining, respectively, and then probed by nanoindentation to characterize their Young's modulus and hardness. Optical and electron microscopy and X-ray diffraction were also used to uncover prestraining-induced microstructure alterations. Precompression in the c* direction to a stress of 45MPa induces elastic uniform straining and causes negligible alteration to the microstructure. Such a prestrained specimen possesses unaltered Young's modulus and hardness. However, the nonuniformly prestrained specimens that were subjected to cantilever bending, even though bending is macroscopically purely elastic, exhibit decreased Young's modulus and hardness, and such reduction depends on the magnitude of bending strains. The Young's modulus decreases by up to 41.0%, from 69.5 to 41.0 GPa at 0 to 6% bending strains, respectively, while the maximum hardness reduction is 40.4%. Such distinction induced by different prestraining modes stems from the bending-induced nonuniform straining as well as the muscovite's unique nanoscale layered structure. Owing to the relatively weaker and reversible electrostatic interlayer bonding, bending-induced strain gradient along the c* direction causes relative interlayer slip and hence bonding switch and, upon unloading, leads to the formation of basal plane corrugation and subsurface blisters. Such structural incoherence and imperfections induced by even elastic bending reduce the Young's modulus and hardness. These findings shed light on the processing-structure-property relationships for other nanostructured multilayers as well as the origin of variability of elastic modulus of muscovites reported in the literature.