CO2 capture and storage (CCS) technology is currently developing rapidly and is being used to sequester large amounts of CO2 aiming to reduce the greenhouse effect. However, CO2 injected into the ground at high temperatures and pressures can become supercritical and interact with rocks. The mechanical properties of rocks interacting with supercritical CO2 are altered, resulting in CO2 leakage. Therefore, it is necessary to study how the mechanical properties of rocks change after interaction with supercritical CO2. In this paper, tight sandstone is used as an experimental sample to study the mechanical properties of sandstone after interacting with supercritical CO2, through high-temperature and high-pressure soaking experiments and nano-indentation experiments. The effects of supercritical CO2 on the micro-mechanical properties of sandstone under different soaking time, temperature and pressure conditions are analyzed. The experimental results show that the statistical mean values of modulus of elasticity and hardness of sandstone decreased after supercritical CO2 soaking, and the longer the soaking time the more serious the deterioration of mechanical properties of sandstone. Supercritical CO2 is capable of dissolving minerals such as clay and feldspar, but the degree of dissolution varies widely and quartz is minimally affected. The modulus of elasticity of quartz decreased by only 14.7% and hardness by 19.4% after 15 days of soaking, compared to a 41.4% decrease in modulus of elasticity and a 48.7% decrease in hardness for clay. It is worth mentioning that the deterioration of mechanical properties in the clay-enriched area is more serious than that of quartz. The creep behavior of the sandstone was similarly affected by supercritical CO2, with the viscous modulus of the three minerals (clay, feldspar, quartz) leveling off after 15 days of soaking. The viscous modulus was decreased by 50.5%, 53.4%, 67.1% and 73.2% compared to the original samples after soaking for 15 days under four soaking conditions. This paper investigates the mechanism of supercritical CO2 interaction with tight sandstone through a series of experiments, providing theoretical support for CCS and CO2 fracturing.