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Abstract Microfluidic valves play a key role within microfluidic systems by regulating fluid flow through distinct microchannels, enabling many advanced applications in medical diagnostics, lab‐on‐chips, and laboratory automation. While microfluidic systems are often limited to planar structures, 3D printing enables new capabilities to generate complex designs for fluidic circuits with higher densities and integrated components. However, the control of fluids within 3D structures presents several difficulties, making it challenging to scale effectively and many fluidic devices are still often restricted to quasi‐planar structures. Incorporating mechanical metamaterials that exhibit spatially adjustable mechanical properties into microfluidic systems provides an opportunity to address these challenges. Here, systematic computational and experimental characterization of a modified re‐entrant honeycomb structure are performed to generate a modular metamaterial for an active device that allows us to directly regulate flow through integrated, multiplexed fluidic channels “one‐at‐a‐time,” in a manner that is highly scalable. A design algorithm is presented, so that this architecture can be extended to arbitrary geometries, and it is expected that by incorporation of mechanical metamaterial designs into 3D printed fluidic systems, which themselves are readily expandable to any complex geometries, will enable new biotechnological and biomedical applications of 3D printed devices.