The large scale extraction of geothermal energy can reduce CO2 emissions. For hot dry rocks, the key to successful utilization depends on the efficiency of reservoir reconstruction. The chemical and thermal stimulation methods are always used in geothermal reservoir reconstruction except in hydraulic fracturing with high fluid injection pressure, which is believed to reduce the seismic hazard by applying before the high-pressure hydraulic fracturing stimulation. However, at the laboratory scale, there are still very limited experimental studies illustrating the combined effects of chemical and thermal stimulation on the permeability and mechanical properties of granite, which is regarded as the main type of hot dry rock. In this paper, comparative stimulation experiments were carried out, including thermal/cold stimulation, CO2 bearing solution hydro-chemical stimulation, combined thermal and CO2 bearing fluid stimulation. By means of nuclear magnetic resonance analysis, permeability test and triaxial compression test, the changes of the micro-structure, permeability and mechanical properties of granite under various stimulation conditions were analyzed. The experimental results show that, compared with the single thermal stimulation and CO2 bearing fluid hydro-chemical stimulation, the superposition effect of thermal and CO2 bearing fluid hydro-chemical stimulation can increase the number of micro-fractures in granite more effectively, thus increasing the permeability, while the elastic modulus and compressive strength decrease. Moreover, the cooling mode on the granite also has a certain influence on the stimulation effect. After water-cooling on the heated granite (300 °C), combined with the CO2 bearing fluid stimulation (240 °C, 20 MPa), the permeability of granite is the highest, increasing by 17 times that of the initial state, and the porosity also increases by 144.4%, while the elastic modulus and compressive strength decrease by 14.3% and 18.4%, respectively. This implies that the deterioration of mechanical properties due to the micro-fractures increased by the thermal and chemical stimulation can enhance the fluid conductivity and heat extraction of granite. The methods in this paper can provide a reference for the combined application of thermal and chemical stimulation technology in artificial reservoir reconstruction of hot dry rocks.