In the medical industry, electrocardiogram (ECG) plays a decisive role in helping people diagnose different diseases. This article applies the designed high-performance differential amplifier to the amplification and denoising of ECG signals, using TSMC 180nm CMOS process and a 1.8V power supply. The differential pair is used to suppress common-mode signals and amplify differential effective signals. The tail current stabilizes the working status of the device and helps achieve a better common mode rejection ratio and linearity. Considering actual manufacturing, the ideal current source in the circuit is replaced with a proportional current mirror (composed using MOS transistors) and a linear resistor, even though the ideal current source works better. This article uses CoolSpice to design schematics and simulations and build different circuits to test various parameters, including gain, input common mode range, DC output swing, etc. What is unique is that the circuit is finally connected to the human body model to observe the ECG results. When optimizing, it is very efficient to use Excel to list and process the data obtained from the simulation in CoolSpice into a line chart. After this, the aspect ratios of transistors and tail current are modified to find excellent differential mode gain, common-mode gain, common-mode rejection ratio, power consumption and bandwidth, which are 46.14dB, −45.46dB, 91.6, 36μW and 77.45MHz respectively. For application scenarios with wider bandwidth and lower power consumption, these parameters are also found, which are 42.74dB, −47.07dB, 89.81, 27μW and 144.36MHz respectively.