MXenes have been widely reviewed as biomedical nanomaterials for sensing, therapy, imaging, drug delivery and tissue engineering. However, most reviews organize MXene studies by biomedical application categories rather than mechanical conditions under which MXene-containing interfaces operate. This leaves an important gap for biomechanical engineering: how MXene-based soft interfaces maintain signal transduction, transport and biological contact when bent, stretched, compressed, hydrated or attached to moving tissues. This mini review addresses that gap by evaluating MXenes as biomechanical interface materials rather than isolated conductive nanofillers or biomedical additives. The rapid growth of MXene-based soft sensors, bioelectronic devices and tissue-contacting systems highlights the need to assess whether these materials can meet translational requirements for stable, deformable, reproducible and biologically compatible interfaces. The review is structured around systems in which mechanical deformation, hydrated transport, electron–ion conduction and biological contact directly affect device function, with representative examples including wearable deformation sensors, electronic skins, hydrogel electrodes, deformable biosensors, wound-contact interfaces and regenerative scaffolds. Applications dominated by drug delivery, cancer therapy, bioimaging, implant coatings or static antibacterial activity are not comprehensively reviewed unless they clarify deformation-dependent transport, tissue contact or interface reliability. We critically compare how surface terminations, oxidation state, flake size, percolation networks, polymer bonding, swelling, modulus matching and biological boundary conditions regulate biomechanical functions. Key challenges include aqueous instability, storage-related degradation, calibration drift, motion artifacts, fatigue, sterilization tolerance and incomplete biological testing. We propose a four-layer interface framework and validation priorities that pair biomechanical testing with cytotoxicity, irritation, inflammatory response and reproducibility assessment.