This study presents a time-interleave and low DC drift long-time continuous photoplethysmography (PPG) signal acquisition system to obtain accurate measurement of heart rate (HR) in real-time. Time-interleave functionality is used herein to minimize the mispositioning issue. Intensity tuning and transimpedance amplifier gain tuning is used herein to acquire a high-quality PPG signal. The front-end analog readout circuit is designed and implemented by using T18 process. The experimental result shows that the design readout system has the DC settling time of 1 second after the motion artifact. The measured current sensing range is 30nA–10uA. The estimated signal to noise ratio is 68dB@1Hz. The backend pre-signal processing incorporates a new convolution-based moving average filter, signal quality index estimator, and a peak-through detector. The non-invasive PPG sensor is applied to the wrist artery of the 40 healthy subjects for sensing the pulsation of the blood vessel. During the measurement, the subject did not drink (alcohol), eat, smoke or workout. The Measurement results shows that the heart rate accuracy and standard error are 95%, and 0.37±1.96bpm, respectively.