Synthetic control circuits have demonstrated their effectiveness in molecular process control. However, current synthetic control circuits counteract the impact of disturbances by error signals. A disturbance suppression strategy that combines a disturbance observer with a controller to achieve better disturbance suppression is presented in this paper. A disturbance observer-based PID control system(DOB-PID) is implemented for the first time using chemical reaction networks(CRNs). The controller parameters are obtained using the flow direction algorithm, which significantly reduces the parameter setting time. The DOB-PID based on CRNs achieves improved disturbance suppression without affecting the setpoint tracking characteristics. To overcome the limitation of the classic disturbance observer relying on the inverse nominal model, a modified disturbance observer-based control system(MDOB) is realized using CRNs. The MDOB-PID eliminates the need for the inverse nominal model in the modeling process. Furthermore, the MDOB-PID control system is combined with a feedforward controller, resulting in a modified disturbance observerbased feedback control system(FDOB). This system effectively decouples the set value following and disturbance suppression characteristics, simplifying the parameter tuning process. Additionally, a FDOB-PID control system is established using DNA strand displacement. The FDOB-PID control system proposed in this paper exhibits lower overshoot and better disturbance suppression compared to existing control systems. Finally, a FDOB-PID exponential gate control system is developed to suppress leakage response in calculation process. This system ensures accurate calculation results even in the presence of a leaky response in the exponential gate.