The durable MXene-based electromagnetic interference (EMI) shielding film with flexible and good mechanical property is significantly desired for the rapid popularity of portable electronics, aerospace, and military. In this study, inspired by the supramolecular interactions in protein structures, we prepare the flexible MXene-based composite film by elaborately designing the cation–π interaction between arginine-modified MXene (A-MXene) and tryptophan-modified epoxidized natural rubber. The resultant MXene-based composite film exhibits remarkable mechanical property. When the loading of A-MXene is only 8 wt.%, the tensile strength reaches 21.57 MPa, and the elongation at break is 880.06%. Moreover, the MXene-based composite film has satisfactory EMI shielding performance. Even after exposure to different conditions, including bending cycle of 7000 times, twisting cycle of 4000 times, ultrasonic treatment in water, soaking in water for 5 days, soaking in ethanol, treatment with HCl (pH = 1), treatment with NaOH (pH = 14), treatment with NaCl (3.5%), treatment at 200 °C for 2 h, treatment at −80 °C for 2 h, cyclic thermal shock, treatment at 85% relative humidity (RH) and 85 °C for 2 h, ultraviolet (UV) irradiation for 2 h, and storage at room temperature for 6 months, the EMI shielding efficiency of the film remains nearly unchanged, suggesting outstanding environmental durability. This work opens an avenue for the development of flexible, robust, and durable MXene-based EMI shielding film used in next-generation electronics.