Traditional hydrogels with poor mechanical properties have the largest barrier for extensive practical applications, such as artificial tendons, cartilage, skin and so on. In this work, a novel design strategy is proposed and demonstrated to improve the mechanical behavior of hydrogels by introducing ductile macromolecular microspheres (MMs) as crosslinking centers. Firstly, the MMs are synthesized, using butyl acrylate as the main component and dicyclopentyl acrylate as an intermolecular crosslinker, by a conventional emulsion polymerization method. Then acrylamide (AM) and hexadecyl methacrylate (HMA) are crosslinked by the MMs in water to form MM crosslinked poly(acrylamide-co-hexadecyl methacrylate) (P(AM/HMA)–MM) hydrogels. From the tensile measurements, the P(AM/HMA)–MM hydrogels exhibit dramatic enhancement of fracture stress sf (0.555 MPa) and fracture strain 3f (5533%) when compared to the original P(AM/HMA) hydrogels. Furthermore, the P(AM/HMA)–MM hydrogels also have excellent puncture resistant properties. Based on traditional mechanisms of rubber-toughened plastics, it is clear that MMs can not only prevent the further development of cracks but can also be stretched to deform and absorb a large amount of energy. It is envisioned that this novel strategy, inspired by a toughening mechanism, will be an effective approach to enhance the mechanical properties and broaden the range of applications for hydrogels