The directional frictional anisotropy of snake-skin-inspired interfaces has great potential to improve the load-bearing performance of offshore uplift pile foundations and other engineering applications. Such interfaces are designed to withstand cyclic loads, including those induced by waves and earthquakes. To investigate the characteristics of directional frictional anisotropy of soil-structure bio-inspired interfaces under cyclic loading, a series of cyclic direct shear tests were conducted using an advanced interface cyclic shear apparatus. The study examined the effects of initial cyclic position, normal stress, bio-inspired interface morphology, and sand density on cyclic shear anisotropy, along with an initial exploration of shear strength characteristics following cyclic loading. The findings revealed that increasing initial position of the cycle and normal stress enhanced shear anisotropy under the cranial-caudal cyclic loading path, while reducing shear anisotropy under the caudal-cranial cyclic loading path. For interfaces at moderate densities, variations in the ratio of interface scale length to height exhibited negligible effects on shear anisotropy. However, as sand density increased, the influence of this ratio on shear anisotropy became more pronounced under the cranial-caudal cyclic shear path, with a slightly increased effect observed under the caudal-cranial cyclic path. Under constant stress conditions, the findings provide valuable insights for the optimization and practical application of bio-inspired interfaces in engineering projects.