<p>Zinc oxide nanoparticles have been synthesized using various techniques, including green chemistry, due to their versatility, cost-effectiveness, and environmentally friendly properties. This study aimed to develop zinc oxide nanoparticles as an anti-inflammatory agent using Alligator pepper (<i>Aframomum citratum</i> K. Schum (Zingiberaceae)) seed extract. To achieve this, the nanoparticles were prepared through the reaction between zinc nitrate and an alkaline aqueous extract of Alligator pepper seeds. The resulting material was then characterized using ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, scanning electron microscopy with energy-dispersive X-ray spectroscopy, powder X-ray diffraction, and transmission electron microscopy. The toxicological profile was evaluated at a limited dose of 2000&#xa0;mg/kg in rats. The anti-inflammatory potential was assessed using methods that included the inhibition of heat-induced egg albumin denaturation, stabilization of red blood cell membranes, and inhibition of carrageenan-induced plantar oedema. Fourier-transform infrared spectroscopy confirmed the presence of secondary metabolites, while scanning electron microscopy revealed multiform aggregates. Transmission electron microscopy visualized small, point-like particles, and energy-dispersive X-ray spectroscopy confirmed the presence of zinc atoms within the synthesized material. The nanoparticles demonstrated high anti-inflammatory activity, with inhibition percentages reaching 86% at a concentration of 1&#xa0;mg/mL in the tested models, red cell membrane stabilization and oedema induction by carrageenan, respectively. These findings suggest that zinc oxide nanoparticles synthesized using Alligator pepper seed extract have significant potential as anti-inflammatory agents.</p>