Abstract: Drying is an ever-increasing demand in both industrial and agricultural fields. However, the traditional drying of heat pumps cannot fully meet the actual requirements of large-scale production, due to the low energy efficiency and serious environmental impacts. It is very necessary to develop an efficient and environment-friendly drying system. In this study, a drying bypass system of a closed-cycle heat pump was proposed for high efficiency using non-azeotropic mixed refrigerants. The heat recovery was optimized to enhance the product quality and the economic performance of the system, particularly with less energy consumption. An experimental and simulation platform was established as the data analysis source. Furthermore, the dynamic and thermodynamic models of the heat pump drying were also developed to clarify the effects of the system air bypass ratio and mixed refrigerant ratio on the system performance. Experimental results show that the drying performance of the system was firstly improved and then declined, as the air bypass ratio increased. Once the air bypass ratio reached 60%, the best performance was achieved to optimize the heat transfer coefficient of the evaporator and the material drying rate. The average temperature was elevated in the drying chamber. The final content of wet basis moisture in the radish was further reduced to 23.4% within the same drying time. In addition, the non-azeotropic mixed refrigerant R32/R600 was introduced to further improve energy efficiency and drying performance. There was a more homogeneous composition of the mixed refrigerant, as the xR32 increased. While the temperature glide decreased gradually. The more uniform thermal driving force was found inside the evaporator, thus improving the heat exchange efficiency and heat transfer coefficient. Furthermore, the maximum coefficient of performance (COP) of the system was achieved at the optimal R32 mass fraction of 0.70. The final content of wet basis moisture in the material decreased to the lowest level, indicating significant energy efficiency. Thermodynamic analysis revealed that the heat transfer losses in the evaporator and condenser accounted for about 50% of the total, where the condenser contributed the most (approximately 32%). The mixed refrigerants significantly improved the heat efficiency of the system. The heat efficiency reached the highest value of 40.37% when the R32 mass fraction was 0.70. There were the 67.5% and 27.0% increase, respectively, compared with the R32 mass fraction of 0.45 and 1.0. Experimental and thermodynamic analysis showed that the drying bypass system of a closed-loop heat pump with the non-azeotropic mixed refrigerant significantly improved the energy efficiency for the better performance of drying in the promising application. This finding can provide important theoretical and technical support to optimize the heat pump drying system.