<p>Nanosponges are novel biomimetic nanoplatforms with immense potential for broad-spectrum toxin sequestration and targeted therapeutic delivery. These porous polymeric nanostructures, designed from cyclodextrins, hyper-cross-linked polymers, or biodegradable copolymers, display high adsorption capacity and modifiable surface chemistry. Recent breakthroughs in cell membrane-coated nanosponges have enabled the development of biomimetic decoy platforms capable of selectively sequestering bacterial toxins, venoms, viruses, and inflammatory mediators, thus inhibiting their binding to host cells and promoting biological clearance. This review compiles the classification, material engineering, fabrication methodologies, and toxin sequestration mechanisms of nanosponges, with a focus on biomimetic detoxification platforms. The translational frontiers of nanosponges, encompassing biosafety, biocompatibility, regulatory hurdles, and relative advantages over traditional antidotes, are critically examined. Notwithstanding the encouraging preclinical results, long-term biosafety, reproducibility, scalable manufacturing, and regulatory standardization continue to pose significant hurdles to clinical translation. In summary, nanosponge-based platforms offer a versatile and toxin-agnostic nanomedicine platform with potential applications in detoxification, infectious disease management, and targeted therapeutic delivery.</p> Graphical abstract