For the high-efficiency thermal conductivity of heat pipes and the unique advantages of thermoelectric cooling, such as noiselessness, environmental protection, and rapid cooling, a new structure of heat pipe-cooled thermoelectric water-chiller is proposed. Based on the finite-time thermodynamics theory and considering various thermoelectric effects including the Thomson effect, a detailed calculation model is established. The influence of key operating parameters and design parameters on the optimal current and optimal performance of the device is analyzed. And the optimal interval of the input current and the optimal interval for coordinating the maximum cooling load and the maximum coefficient of performance (COP) are given. The optimization results show that when the temperature difference is 20K and the current is 2.5A, the maximum cooling load and maximum COP are improved by 55.3% and 47.0% after optimization, reaching 29.49W and 1.47, respectively.