Abstract Uncertainty relations and quantum entanglement are pivotal concepts in quantum theory. Beyond their fundamental significance in shaping our understanding of the quantum world, they also underpin crucial applications in quantum information theory. In this article, we investigate entropic uncertainty relations and entanglement detection with an emphasis on quantum measurements with design structures. On the one hand, we derive improved Rényi entropic uncertainty relations for design-structured measurements, exploiting the property that the sum of powered (e.g., squared) probabilities of obtaining different measurement outcomes is now invariant under unitary transformations of the measured system and can be easily computed. On the other hand, the above property essentially imposes a state-independent upper bound, which is achieved at all pure states, on one’s ability to predict local outcomes when performing a set of design-structured measurements on quantum systems. Realizing this, we also obtain criteria for detecting multi-partite entanglement with design-structured measurements.