Smart clothes equipped with flexible sensing systems provide a comfortable means to track health status in real time. Although these sensors are flexible and small, the core signal-processing units still rely on a conventional printed circuit board (PCB), making current health-monitoring devices bulky and inconvenient to wear. In this study, a printed fabric-based hybrid circuit was designed and prepared—with a series of characteristics, such as surface/sectional morphology, electrical properties, and stability—to study its reliability. Furthermore, to verify the function of the fabric-based circuit, simulations and measurements of the circuit, as well as the collection and processing of a normal adult’s electrophysiological signals, were conducted. Under 10,000 stretching and bending cycles with a certain elongation and bending angle, the resistance remained 0.27 Ω/cm and 0.64 Ω/cm, respectively, demonstrating excellent conductivity and reliability. Additionally, the results of the simulation and experiment showed that the circuit can successfully amplify weak electrocardiogram (ECG) signals with a magnification of 1600 times with environmental filtering and 50 Hz of industrial frequency interference. This technology can monitor human electrophysiological signals, such as ECGs, electromyograms (EMGs), and joint motion, providing valuable practical guidance for the unobtrusive monitoring of smart clothes.