In order to survive in nature, living systems undergo highly defined morphological evolution to adapt to environmental changes. For example, sponges, [1] aquatic animals of the phylum Porifera, possess bodies full of pores, channels, and chambers, through which a water flow circulates, to bring food and oxygen, and to remove wastes. Therefore, sponges represent a biological paradigm for storage and release of water in a so-called porous system. Possessing similar unique characteristics of natural ones, biomimetic systems have become more and more appealing. [2][3][4][5][6][7] Artificial sponges, which resemble the aforementioned porous and elastic animal sponges, have been This study describes the fabrication of bioinspired mechano-regulated interfaces (MRI) for the separation and collection of oil spills from water. The MRI consists of 3D-interconnected, microporous structures of sponges made of ultrasoft elastomers (Ecoflex). To validate the MRI strategy, ecoflex sponges are first fabricated with a low-cost sugar-leaching method. This study then systematically investigates the absorption capacity (up to 1280% for chloroform) of the sponges to different oils and organic solvents. More importantly, the oil flux through the as-made sponges is controlled by mechanical deformation, which increases up to ≈33-fold by tensile strain applied to the sponge from 0 to 400%. On the basis of MRI, this study further demonstrates the application of ecoflex sponges in oil skimmers for selective collecting oil from water with high efficiency and durable recyclability. The as-developed MRI strategy has opened a new path to allow rational design and dynamical control toward developing high performance devices for oil permeation and selective collection of oil spills from water.