In recent years, there have been increasing research interests in investigating the compression and ballistic responses of metal-ceramic hybrid structures, mainly making use of the synergistic effects of conventional metal honeycomb structures and infilled ceramic matrix materials. In this paper, a novel hybrid auxetic re-entrant metal-ceramic lattice is designed and manufactured to overcome the intrinsic conflicts between the strength and toughness of architected mechanical metamaterials, synergistic effects of auxetic re-entrant metal honeycombs and infilled ceramic materials are experimentally and numerically studied, and auxetic deformation features and failure modes are characterized with the digital image correlation (DIC) technique as well. It was found that (1) the infilled ceramic matrix of conventional honeycomb frames only endure longitudinal compression or impact loading along the external loading direction, while auxetic metal re-entrant honeycomb components endure both longitudinal and transverse loading due to the negative Poisson′s ratio effect and (2) the collaborative effects of infilled auxetics and the constraint frames’ hybrid structure dramatically moderate the stress concentration state and improve the impact resistance of single-phase ceramic materials. Our results indicate that the auxetic hybrid design exhibits promising industrial application potentials for blast protection engineering.