Engineering conventional hydrogels with muscle‐like anisotropic structures can efficiently increase the fatigue threshold over 1000 J m−2 along the alignment direction; however, the fatigue threshold perpendicular to the alignment is still as low as ≈100–300 J m−2, making them nonsuitable for those scenarios where isotropic properties are desired. Here, inspired by the distinct structure–properties relationship of heart valves, a simple yet general strategy to engineer conventional hydrogels with unprecedented yet isotropic fatigue resistance, with a record‐high fatigue threshold over 1,500 J m−2 along two arbitrary in‐plane directions is reported. The two‐step process involves the formation of preferentially aligned lamellar micro/nanostructures through a bidirectional freeze‐casting process, followed by compression annealing, synergistically contributing to extraordinary resistance to fatigue crack propagation. The study provides a viable means of fabricating soft materials with isotropically extreme properties, thereby unlocking paths to apply these advanced soft materials toward applications including soft robotics, flexible electronics, e‐skins, and tissue patches.