<p>Transition metal carbides, nitrides and carbonitrides (MXenes) have attracted considerable attention since they were first reported in 2011. With their metallic-level electrical conductivity, outstanding mechanical properties and abundant surface terminal groups, MXenes have broad application potential in aerospace, energy storage and biomedicine. However, translating the superior intrinsic properties of monolayer MXene nanosheets into macroscopic nanocomposites remains challenging. This Review systematically elucidates the development of high-performance MXene nanocomposites through bioinspired confined assembly strategies. We discuss the advanced characterization of voids formed during the wet chemical assembly of MXene nanosheets and clarify the mechanisms underlying their formation. On this basis, we introduce bioinspired confined assembly strategies to reduce porosity and enhance the efficiency of interlayer load transfer, which markedly improve the macroscopic mechanical and electrical properties of MXene nanocomposites. We further outline large-scale fabrication methods for bioinspired confined MXene nanocomposites. We discuss the properties and some representative applications of MXene nanocomposites, including electromagnetic interference shielding, bone regeneration and artificial muscles. Finally, we provide our perspectives for future research directions for bioinspired confined MXene nanocomposites.</p>