Efficient decalcification of dolomite-rich magnesite resources typically requires high-performance depressants. This study introduces a novel dolomite depressant, synthesized by combining sodium phytate (SP) and sodium silicate (SS), and evaluates its effectiveness in flotation. The impact of the combined depressant on the mineral surface properties and pulp characteristics during flotation was assessed using techniques, including contact angle measurement, bubble-particle wrap angle testing, turbidity testing, microscopy, SEM-EDS, and XPS. The results show that the depressant selectively adsorbs onto calcium sites on the dolomite surface, thereby increasing its hydrophilicity. It also acts as a dispersant, reducing particle agglomeration and improving pulp dispersion. Electrostatic potential (ESP) and average local ionization energy (ALIE) calculations were performed to identify the reaction sites, while molecular dynamics (MD) simulations and the Independent Gradient Model (IGM) were used to analyze the depressant-mineral interactions. The findings reveal that the SP-SS combined depressant self-assembles primarily through hydrogen bonding. The interactions between the depressant and the dolomite surface are predominantly driven by hydrogen bonding, coordination bonding, and steric hindrance, with SP playing a key role. This study highlights the potential of the SP-SS combined depressant for effective decalcification, offering valuable insights for optimizing flotation processes.