Inorganic nanozymes hold promise for biomolecule sensing but face challenges like complex fabrication, toxicity, and low sustainability, limiting their use. To overcome these, a sustainable organic nanozyme (OA nanozyme) was created using amino acids and a biocompatible polymer for effective histamine detection. The OA nanozyme exhibits peroxidase-like activity and was fabricated through a single chelation/polymer entanglement method, enabling rapid production (within 3 h) with uniform morphology (≤100 nm diameter) and a negative surface charge at neutral pH. It shows decent kinetic performance (Km = 0.009 mM for H 2 O 2 ) and biocompatibility, making it suitable for biological applications. The OA nanozyme achieved high sensitivity for histamine detection (LOD: 21.37 pgmL −1 ) with excellent selectivity and specificity against related molecules. The system's ability to detect histamine in real food samples (e.g., spinach) was also confirmed. These findings indicate that the OA nanozyme holds significant potential for broader applications in food safety and quality assurance. • Amino-acid based, organic nanozyme (OA nanozyme) having peroxidase-like catalytic activity. • Customized particle fabrication procedure for homogenous nanozyme generation. • Engineering surface-mediated, effective histamine sensing system. • Affordable analytic sensitivity/selectivity, with cost-effectiveness below 1USD/set.