This paper introduces a medium voltage direct-current (MVDC) system for large spacecraft megawatt-scale (MW) power and propulsion systems intended for interplanetary transport, including missions to the Moon and Mars. The proposed MVDC system includes: (i) A nuclear electric propulsion (NEP) that powers a permanent magnet (PM) generator whose output is rectified and connected to the MVDC bus. (ii) A solar photovoltaic (PV) source that is interfaced to the MVDC bus using a unidirectional boost DC-DC converter. (iii) A backup battery energy storage system (BESS) that connects to the MVDC bus using a bidirectional DC-DC boost converter. (iv) A dual active bridge (DAB) converter that controls the power to the spacecraft’s electric thruster. The NEP serves as the main power source for the spacecraft’s electric thruster, while the solar PV and BESS are intended to provide power for the payload and spacecraft’s low-voltage power system. The paper will (i) provide a review of the spacecraft MVDC power and prolusion system highlighting state-of-the-art main components, (ii) address the control of boost converters for the PV and BESS sources and the DAB converter for the thruster, and (iii) propose an uncertainty and disturbance estimator (UDE) concept based on current control algorithms to mitigate MVDC instability due to unpredictable factors and external disruptions. The proposed UDE can actively estimate and compensate for the system disturbance and uncertainty in real time, and thus, both the system tracking performance and robustness can be improved. Simulation studies have been conducted to substantiate the efficacy of the proposed schemes.