In order to improve the comfort of the living environment, the thermal performance and temperature–humidity regulation of the exterior walls of two timber-framed structure buildings is theoretically calculated and experimentally studied in this study. Both of the two buildings are located in Nanjing, China, the hot-summer and cold-winter zone. Then WUFI is used to simulate and predict the changes of temperature, relative humidity, and water content of the two timber-framed structure buildings, to strengthen the theoretical analysis of the thermal and humidity coupling of the external walls, and to propose an optimal design scheme for the insulation and temperature and humidity regulation of the external walls. The main results show that the tested thermal conductivity is basically consistent with the predicted value, which prove that WUFI simulation can effectively predict the thermal insulation performance of the external wall. The two timber-framed structure buildings are both suitable for the cold areas, and the reasonable optimization of the design of the structure is the key to the insulation of the building wall. Timber-framed structure is proved to have good temperature–humidity regulation effect. The moisture content of the two timber-framed structure buildings is stable, and the annual temperature and winter humidity are within the appropriate humidity range, which indicates that the wall design is suitable for Nanjing hot-summer and cold-winter climate zone. Four types of wall structure indoor mold spore germinations are less likely, which is not easy to produce the mold. The above research aims to optimize the design of the energy-saving wall of the timber-framed structure and create a comfortable and healthy living environment.
