Soil–structure interfaces typically exhibit a shear behavior that is independent of the direction of relative displacement due to symmetry in the solid material's surface profile. This experimental study investigates the interface shear behavior of surfaces with asymmetric profiles inspired by the scales of snake skin. The results of shear box interface tests on two sandy soils indicate that the peak and residual interface shear strengths and dilatancy are greater when the soil is displaced against the sharp edges of the asperities (cranial direction) than when the soil is displaced along the asperities (caudal direction). The experimental results indicate that the effect of asperity geometry on the interface shear response can be captured with the ratio of asperity length to asperity height (L/H). Analysis of the stress–dilatancy behavior indicates that interfaces with a relatively short asperity length follow a classical flow rule developed for soils. However, the relationship between the mobilized stress ratio and the dilatancy rate is shown to be a function of the shearing direction and asperity geometry. Implementation of snake skin-inspired profiles on the surface of geotechnical structures may provide benefits in performance and efficiency during installation and service life. In general, the results of this study indicate the behavior of the soil-structure interfaces sheared in the cranial direction is similar to that of interfaces between soil and fully rough surfaces. In contrast, the behavior of the soil-structure interface sheared in the caudal direction shares characteristics with that of interfaces with smooth surfaces, including the mobilization of smaller a interface strength and dilation.