On Mars, liquid water may form in regolith when perchlorate salts absorb water vapor and dissolve into brine, or when ice-salt mixtures reach their melting temperature and thaw. Brines created in this way can chemically react with minerals, alter the mechanical properties of regolith, mobilize salts in the soil, and potentially create habitable environments. Although Martian brines would exist in contact with regolith, few studies have investigated how regolith alters the formation and stability of brines at Mars-relevant conditions. To fill this gap, we studied magnesium perchlorate brine in a Martian regolith simulant at salt concentrations up to 5.8 wt.%. We measured the water mass fraction and water activity between 3 and 98% relative humidity at 25 °C using the isopiestic method, and monitored salt and ice crystallization between −150 °C and 20 °C with differential scanning calorimetry. Results show that regolith inhibits salt and ice crystallization, allowing water to form and persist at much colder and drier conditions than pure brine. Remarkably, in several samples, neither salt nor ice crystallized at any conditions. These results suggest that brines could exist in regolith for longer periods of the Martian year than previously thought, and could persist indefinitely under certain conditions. By retaining water, inhibiting salt and ice crystallization, and maintaining habitable water activity, briny regolith may be a more favorable environment for life than pure brine alone. These findings indicate the critical importance of brine–regolith interactions for understanding the properties, evolution, and potential habitability of Mars’s surface.