A new photoplethysmography (PPG) module is designed, optimized, and fabricated in this study to obtain quality PPG signal for high-accuracy bio-sensing. The module contains four light emitting diodes (LEDs) in wavelengths of 530, 660, 850, and 940 nm and a photo-diode (PD). The distances between LEDs and PD are optimized for quality PPG signals via maximizing the ratios of pulsatile (ac) to non-pulsatile (dc) components in PPG waveforms. The optimization is carried out based on an establishment of a complete optical model that simulates well optics under the user's skin based on Beer–Lambert law. In results, the optimal LED/PD distances that lead to maximal ac/dc ratios of PPGs for different wavelengths are derived. With the optimal LEDs/PD distances in hand, a new PPG module is designed and fabricated subsequently, and further installed in a hand-held blood pressure (BP) sensing device for performance validation. Based on experimental results, for the PPG module, an ac/dc ratio of 8.02% is achieved by the proposed PPG module as opposed to 6.74% and 6.90% by two other commercial modules. As for sensing BP based on reflective pules transient time, the error is controlled well with the mean difference (MD) and standard deviation (SD) as −1.16 ± 5.38 (MD±SD) and −0.53 ± 1.92 mmHg, respectively, for systolic blood pressure and diastolic blood pressure. The resulted accuracy successfully categories the developed PPG sensor among the bests by Association for the Advancement of Medical Instrumentation and British Hypertension Society.