This study aimed to understand the effects of expressway construction on the soil environment in the karst area of Guangxi. To achieve this, the impact of expressway construction on soil physicochemical properties, heavy metal content, organic carbon, and nitrogen isotope composition, along with characteristics, were determined. Soil samples were collected from the east and west sides of the unopened Hezhou-Bama Expressway (Laibin to Du'an section) after construction. Seven primary heavy metals, including Cu, Pb, Zn, Cd, As, Hg, and Mn, soil physicochemical properties, organic carbon, and nitrogen isotopic compositions were detected. The soil accumulation index (Igeo), contamination factor (CFi), and pollution load index (PLI) were used to analyze the degree of pollution. The study found that the soil moisture content, organic matter content, and the mass fraction of available nutrients decreased due to the disturbance of soil structure and the change of vegetation types during construction. However, the content of heavy metals in the soil did not exceed the soil pollution risk control standard of soil environmental quality construction land. The δ13C and δ15N in soil on both sides showed a heavy characteristic, mainly due to the reduction of soil organic matter, microorganisms, and fixed nitrogen caused by construction. The study also found that with the increase in highway operation time, the pollution potential of soil heavy metals on both sides of the highway will continue to increase. These findings provide an essential theoretical basis for preventing and controlling heavy metal pollution on expressways in Guangxi and support the restoration of the ecosystem on expressways' roadside slopes.