We propose a novel design methodology consisting of bio-inspired (BI) and interleaved layups to develop hybrid carbon fibre-reinforced polymer (CFRP) composite structures for improved high-velocity impact (HVI) performance. Firstly, we apply a BI helicoidal design method consisting of various pitch angles (considering both thick- and thin-ply CFRP) to develop BI monolithic CFRP laminates. Secondly, we apply the interleaving design method to develop BI hybrid CFRP-based laminates interleaved with blocks of BI Zylon fibre-reinforced polymers through the thickness. We evaluate their response and compare it with traditional quasi-isotropic (QI) hybrid bulk layups. In addition to hybridising with Zylon, we apply titanium (Ti) foils to both the monolithic and hybrid CFRP-based laminates to investigate and compare their response. For all our hybrids, we kept the ratio of the hybridising material(s) to be less than 50% to ensure suitable in-plane mechanical properties and aimed at a target areal weight of 0.95 g/cm2. We also manufactured QI thick- and thin-ply monolithic CFRP laminates as baselines. We tested all laminates at 170 and 210 m/s and studied their response and failure modes. Our results show that the average energy dissipation of the QI monolithic thin-ply baseline improved by up to 22% by changing the layup from QI to BI, and by about 118% by changing the baseline QI layup to BI hybrid interleaved. Post-mortem analysis reveals that there are additional failure mechanisms activated in the BI hybrid interleaved layup with respect to the baseline.