Carbon dioxide sequestration or utilization in low-permeability reservoirs helps the national “dual carbon” strategy. Carbon dioxide injection is also one of the key development technologies to promote efficient utilization of such reservoirs. Supercritical CO2 is used in low-permeability sandstone gas drive, huff and puff, fracturing and energy enhancement processes. Existing experimental studies have shown that CO2 injection promotes dissolution and crack formation in such low-permeability sandstone reservoirs, which may increase porosity and permeability. However, there is also controversy over its use, because it may also cause reservoir damage. The study investigated the effect of high-temperature high-pressure (50–70 MPa, 55–95 ℃) supercritical CO2 on the micro pore throat structure and macro permeability of low-permeability sandstone of C6 reservoir through carbon dioxide immersion experiments and theoretical analysis. It is found that supercritical CO2 plays a role in increasing porosity, but permeability may increase or decrease. There are differences in the improvement of reservoir physical properties under different temperature and pressure environments, that is, the physical properties of rock during CO2 injection will vary with the temperature and pressure changes within the action range. The action of supercritical CO2, dissolution phenomena of minerals such as potassium feldspar and chlorite were investigated, and quartz precipitation was formed in some positions. The maximum peak of the pore size distribution curve shifted to the right, and a single pore structure gradually evolved into multiple pore structures. The nitrogen adsorption curve showed fluctuating changes (both upward and downward shifts were found). The envelope area of hysteresis ring by adsorption–desorption curve increased first and then decreased with the supercritical CO2 pressure, and continued to increase with the supercritical CO2 temperature. The research indicated that inappropriate parameters for supercritical CO2 injection, water rock interaction between formation rock fluid CO2, and particle transport during CO2 injection may all cause formation damage. It is beneficial for providing theoretical guidance for the rational development of CO2 mineralization, storage, and application in low-permeability oil reservoirs.