In this paper, CMOS based optimized two stage differential amplifier circuit for convenient biomedical signal conditioning system is presented. A low-power, low noise & high CMRR differential amplifier is designed for portable ECG signal conditioning using MOS based low pass filter with stacked transistors. The stack transistors with MOS which is connected at output terminal optimize the design for ECG signal conditioning and other biomedical device signal conditioning. The presented amplifier is designed with standard 45nm CMOS process technology at a 0.85 V supply voltage. The simulation results are derived using Cadence Analog Virtuoso Spectre Simulator. The simulation results show that the presented differential amplifier has a common-mode rejection ratio (CMRR) of 178dB at 100Hz, power supply rejection ratio (PSRR) of 68 dB and power dissipation of 1.5μW. The input referred (IR) noise is 3.83μV/√f and slew rate is 11volt/μsec. These obtained performance parameters is better and efficient compared to conventional differential amplifier. The noise performance is improved using proposed design compared to previous designed differential amplifier.