[Objective] To safeguard freshwater intake security in the Yangtze River Estuary against frequent saltwater intrusion, this study aims to identify an optimal freshwater replenishment scheme that balances saltwater suppression effectiveness with water resource utilization efficiency. [Methods] To address extreme saltwater intrusion resulting from the combined effects of low runoff and strong tidal dynamics, a two-dimensional coupled hydrodynamic and salinity transport model was developed. Numerical scenarios incorporating various replenishment discharges and durations were designed based on actual dispatch strategies. Key evaluation indicators included the spatiotemporal distribution of salinity isolines and the duration of the available water intake window. The effectiveness of saltwater suppression was comprehensively evaluated by quantifying the variations in environmental responses under different replenishment strategies. [Results] Simulation results indicated that, influenced by the complex topography of the Yangtze River Estuary, the spatial distribution of replenishment effects exhibited non-uniform characteristics. Under cascade replenishment schemes, the seaward retreat rate of salinity isohalines was approximately 1.52-1.59 km/(500 m³/s) in the North Channel and 1.75-1.92 km/(500 m³/s) in the South Channel. Salinity levels at the intakes of Chenhang Reservoir and Qingcaosha Reservoir showed an overall decreasing trend, with decay rates of approximately 0.03‰/(500 m³/s) and 0.05‰/(500 m³/s), respectively. Intake salinity exhibited an approximately linear relationship with replenishment discharge, with the Qingcaosha Reservoir demonstrating a relatively higher degree of responsiveness. In contrast, the relationship between the available water intake window and the replenishment duration was non-linear, exhibiting characteristics of marginal utility. The findings suggested that maintaining a replenishment discharge of approximately 9 900 m³/s might provide strong assurance for water intake, while a replenishment duration of around 13 days was likely to achieve optimal benefits. Furthermore, strong offshore winds tended to amplify frontal saltwater intrusion in the North Channel. [Conclusion] Increasing discharge from the Three Gorges Reservoir effectively suppresses saltwater intrusion and contributes positively to mitigating salinity hazards in the Yangtze River Estuary. However, replenishment performance is constrained by multiple factors, including the replenishment mechanisms and offshore wind fields. Optimization of replenishment strategies should consider both discharge magnitude and duration, as prolonged duration does not necessarily result in proportional benefits. Moreover, compared with the North Branch and South Channel, replenishment effects in the North Channel and at Qingcaosha Reservoir are more susceptible to wind field influences. These findings provide technical support for decision-making on water replenishment scheduling during extreme dry seasons.