With the rapid development of key projects in China, such as West-to-East Gas Transmission and South-to-North Water Diversion, buried pipelines will inevitably pass through the mountainous area and are affected by regional topography and landforms. However, the interaction mechanism between slope and pipelines is still relatively unclear. In this study, the model tests on sandy slope-pipe interaction under loading are carried out in laboratory based on distributed strain sensing (DSS) and particle image velocimetry (PIV) technologies. The factors influencing the bearing capacity of the foundation are investigated. The failure characteristics of the slope and the structural responses of the buried pipeline are also explored. The research results show that: (1) The slope foundation has undergone three stages: elastic compaction, local shear and overall destruction. The foundation shows asymmetrical wedge-shaped failure pattern. (2) With the increase in slope angle, the ultimate bearing capacity of the foundation decreases. Under the same slope angle, the presence of pipeline reduces the ultimate bearing capacity of the slope foundation. (3) With the increase in slope angle, the influence of the pipeline on the slope failure mechanism increases. (4) Under the loading of the slope, the circumferential strain in the cross-section of the buried pipe is “elliptically” distributed, and an ellipticity calculation formula and a simplified calculation model of the soil resistance around the pipe circumference are proposed. This study can provide a reference for the deformation control and structural design of buried pipelines in sandy slopes.