Pulse wave contains detailed information about the human cardiovascular system and is associated with various physiological changes. A fingertip-like pulse sensor based on a piezoresistive sensor was constructed to extract weak pulse signals with lossless performance. In the sensing mechanism, the external force was deformed through the flexible film and transmitted to the Wheatstone bridge to realize the force–electric conversion measurement. The sensor experiments revealed that the sensor’s performance had excellent linearity ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${R}^{2}>0.9999$ </tex-math></inline-formula> ), low hysteresis (<1%), and high sensitivity (0.04 V/kPa). A pulse acquisition device based on pulse measuring was developed and applied to clinical practice for pulse signal measurement. Genuine pulse signals were obtained by removing high-frequency noise and baseline drift from the original pulse signal. A total of 55 volunteers aged 20–85 years with different health conditions were recruited, and eight were previously diagnosed with arrhythmia. Results demonstrated that the pulse period (PP) interval presented three different distribution patterns. Pulse signals obtained at different locations with various pressures showed potential application in digital pulse diagnostics.