Wellbore instability and formation collapse are crucial issues in the process of well excavation in the oil industry under extreme salinity and high-temperature conditions. This study demonstrates that a salt-responsive zwitterionic polymer brush (NS-DAD) based on modified nanosilica as a fluid-loss additive utilizing the anti-polyelectrolyte effect in water-based drilling fluids (WDFs) to overcome the wellbore instability caused by the failure of polyelectrolytes at extreme salinity and high temperature. Additionally, a nonionic polymer brush (NS-D), an anionic polymer brush (NS-DA), and a cationic brush (NS-DD) were also prepared for comparison. Compared with NS-D, NS-DA, and NS-DD, NS-DAD exhibited the anti-polyelectrolyte phenomenon, in which the sodium chloride electrolyte shields the electrostatic interaction in the molecular chain of the polyzwitterion and the molecular structure changes from a collapsed sphere to a more open helix. Macroscopically, NS-DAD exhibited a higher viscosity than NS-D, NS-DA, and NS-DD in saturated salt-based mud (SSBM). A typical "star-net" structure was observed between NS-DAD and the bentonite layer. Energy-dispersive spectroscopy (EDS) analysis of filter cakes showed that NS-DAD could significantly reduce the content of chloride and sodium ions in the bentonite layer. Therefore, compared with NS-D/SSBM, NS-DA/SSBM, and NS-DD/SSBM, NS-DAD/SSBM had excellent theological properties, thermal stability, less fluid-loss volume, and thinner filter cake under extreme salinity and high-temperature conditions. The fluid-loss additive can be used to reduce the fluid-loss volume of WDFs in harsh reservoir conditions of high temperature and high salinity.