Experiments and molecular dynamics simulations show that the dehydration-induced actuation of nanoporous tripeptide crystals is a result of pore contraction caused by the strengthening of the water hydrogen-bonding network inside the pore, which creates mechanical stress that deforms the crystal lattice. Water-responsive materials undergo reversible shape changes upon varying humidity levels. These mechanically robust yet flexible structures can exert substantial forces and hold promise as efficient actuators for energy harvesting, adaptive materials and soft robotics. Here we demonstrate that energy transfer during evaporation-induced actuation of nanoporous tripeptide crystals results from the strengthening of water hydrogen bonding that drives the contraction of the pores. The seamless integration of mobile and structurally bound water inside these pores with a supramolecular network that contains readily deformable aromatic domains translates dehydration-induced mechanical stresses through the crystal lattice, suggesting a general mechanism of efficient water-responsive actuation. The observed strengthening of water bonding complements the accepted understanding of capillary-force-induced reversible contraction for this class of materials. These minimalistic peptide crystals are much simpler in composition compared to natural water-responsive materials, and the insights provided here can be applied more generally for the design of high-energy molecular actuators.