The research area of the wearable electrochemical sensors is increasingly growing which are valuable for healthcare and fitness applications owing to their simplicity of operation, low-cost, and compact size. In this work, optimizing of programmable analog front-end for fully integrated wearable sweat sensor is proposed. The proposed system can detect glucose, lactate, sodium, potassium at the same time with low-power consumption which is suitable for continuous real-time sweat sensing system. The average power consumption of analog front-end in the proposed system is less than 2 mW at 3.3 V supply voltage.