Nature has inspired researchers over the past years to address a wide range of engineering challenges by mimicking living organisms due to their unique mechanisms. In structural engineering, bio-inspired systems have been utilized in previous studies as energy absorbers; however, their uses as blast-resistant structures are still very limited. The current study proposes three bio-inspired steel blast mitigation systems that can effectively reduce the pressure values behind their panels based on mimicking the structural frameworks of i) falcon's nostril; ii) orca's jaw; and iii) pangolin-armadillo scales. In this respect, the study discusses the morphology of such organisms and their corresponding integrated blast mitigation mechanisms that include interlocking bearings, deviations and reflections, element deformations, and suppressive system interactions. The blast performance of the developed bio-inspired systems is then numerically compared to conventional steel systems (solid and corrugated panels). These comparisons include the pressure values and the transmitted impulse at different distances behind the panels as well as kinetic and internal energy histories. The proposed mitigation mechanisms are also verified through different response parameters such as wave distributions, material strains and panel deformations. Finally, performance charts are presented for each system to illustrate the pressure values behind the panels for different scaled distances (from 0.2 m/kg1/3 to 0.5 m/kg1/3), thus showing different protection levels. The results demonstrate that the developed systems can reduce the maximum pressure values of the explosions relative to the conventional panels by averages of 65%, 59%, and 74%, respectively. •The study introduces three bio-inspired blast mitigation systems that can reduce the pressure values behind their panels.•The proposed steel panels are based on the mimicry of the falcon's nostril, orca's jaw, and pangolin-armadillo scales.•The blast performance of the three developed bio-inspired systems is numerically compared to conventional steel systems.•Performance charts are presented to illustrate the protection levels of the systems under different explosion scenarios.•The results can be utilized in future studies to address other complex engineering challenges using bio-inspired systems.