Understanding the effects of surface nanostructures on fluid flow in micro- and nano-channels is highly desirable for micro/nano-electro-mechanical systems. By way of equilibrium and non-equilibrium molecular dynamics simulations, wetting on nano-structured surfaces and liquid flow in nano-channels with structured surfaces are simulated. The surfaces show dual effects on the boundary slip and friction of the liquid flow in nano-channels. Generally, the nanostructures enhance the surface hydrophilicity for a hydrophilic liquid-solid interaction, and increase the hydrophobicity for a hydrophobic interaction. Simultaneously, the nanostructures distort the nanoscale streamlines of the liquid flow near the channel surface and block the flow, which decreases the apparent slip length. The twofold effects of the nanostructures on the surface wettability and the hydrodynamic disturbance result in a non-monotonic dependence of the slip length on the structure’s size. However, the surface structure may lead to a very high contact angle of about 170° in some cases, which cause the surface show super-hydrophobicity and lead to a remarkable velocity slip. The surface nanostructures can thus be applied to control the friction of micro- and nano-flows. In addition, the gaseous flows in micro- and nano-channels with structured surfaces are simulated. The geometry of the surface is modeled by triangular, rectangular, sinusoidal and randomly triangular nanostructures respectively. The results show that the velocity slips, including negative slip, depend not only on the Knudsen number but also the surface structure. The impacts of the surface nanostructure and the gas rarefaction are strongly coupled. In general, the slip length of a gaseous flow over a structured surface is less than what predicted by the Maxwell model, and depends not only on the Knudsen number but also the size of the surface nanostructures.