Abstract: In-depth profile control is a crucial technique employed to enhance oil recovery in fractured-vuggy carbonate reservoirs. However, it is a challenge to achieve in-depth profile control. In this paper, two types of organic gel systems, namely s-MPG and MSRG, tailored for fractured-vuggy reservoirs with 140 °C and 22 × 104 mg/L have been developed. FTIR was used to analyze the functional groups of s-MPG and MSRG. Additionally, the quality retention rates of s-MPG and MSRG were assessed using TG-DSC, yielding results of 92.85% and 92.65%, respectively. The dilution rates of s-MPG and MSRG are found to be 18.69% and 26.69%, respectively, demonstrating excellent compatibility and adaptability. The enhancement performance depends on the synergistic effect that the anti-dilution s-MPG effectively separates bottom water, while high-strength MSRG separates the oil layer. Moreover, the EOR performances of s-MPG synergy with MSRG in various types of fractured-vuggy carbonate models were also evaluated. The highest oil recovery of 12% is achieved in fracture network model. Laboratory results indicate that the synergistic combination of s-MPG and MSRG for water plugging in fractured-vuggy carbonate reservoirs results in a more effective enhancement of oil recovery compared to using a single gel system for plugging. Finally, the s-MPG synergy with MSRG has been applied in actual fractured-vuggy carbonate reservoirs. As expected, the water cut of typical well is reduced from 100% to 30% and the increased oil production is 1142 t totally. Therefore, this study presents a novel approach to achieving in-depth profile control by leveraging the synergistic effect of s-MPG with MSRG in fractured-vuggy carbonate reservoirs.