Redispersion behavior recovers the important features of nanomaterials and thus holds great promise for exciting applications of nanomaterials in different fields. In contrast to the redispersion of nanoparticles, which is mainly determined by surface chemistry, the redispersion of 2D nanosheets could be more complicated and is not well understood. In the present study, the redispersion behavior of 2D NMs was investigated by selecting representative nanosheets, MoS2, graphene oxide and their derivatives with both experimental methods and molecular dynamics (MD) simulations. The good agreement between experiments and MD simulations suggested that the redispersion in response to surface chemistry was regulated by the alignment configurations of the nanosheets. More importantly, we revealed that the difference in the hydrophilicity properties is responsible for the distinctive separation distances of the 1T and 2H MoS2 nanosheets. Appropriately adjusting the alignment configuration of the nanosheets can alter the effect of surface hydrophilicity on the redispersion behavior. Based on these fundamental findings, we identified three distinctive zones for the redispersion tendency of the 2D nanosheets with different surface hydrophilicity, Hamaker constants and intersheet contacts. As one of the implications, the results serve as a prescreening for the stability of the 2D restacking-based membrane. For the first time, the study systematically reported the interplay of intersheet configuration and surface chemistry in the redispersion of nanosheets, which provides a theoretical foundation for the processing and applications of 2D nanomaterials.