Since the ventral body side of snakes is in almost continuous contact with the substrate during locomotion, their skin is presumably adapted to generate propulsion (high friction) and simultaneously slide along the substrate at rather low friction. In this study, the microstructure of ventral scales is shown and its influence on frictional properties was investigated by the use of scanning electron microscopy and microtribometry. To analyze the role of the system stiffness on the frictional anisotropy, two different types of sample cushioning (hard and soft) were tested while sliding in four different directions. Frictional anisotropy for both types of sample cushioning was demonstrated, however, the anisotropy was much stronger expressed in the soft cushioned sample. This effect is explained by the stronger ability of the soft-cushioned microstructure to slip along (or resist) the micro- and nanoscale features of the substrate, if compared with the hard-cushioned one.