© 2021, African Association of Insect Scientists.Abstract: Organic–inorganic hybrid nanoflowers have gained considerable attention over the last years due to their morphologies, enhanced enzymatic activities, and relatively high stability. The framework of these hybrid nanostructures has been associated with the formation of Cu3(PO4)2.3H2O (pure copper phosphate nanoflowers). In this study, we investigated the formation of pure copper phosphate nanoflowers (p-CPnfs), and their effects on hemocytes and enzymatic responses in Galleria mellonella (Lepidoptera: Pyralidae) as a model organism. Therefore, the effects of p-CPnfs on G. mellonella hemocytes and on the activities of hemolymph acetylcholine esterase (AChE), superoxide dismutase (SOD), and catalase (CAT) enzymes were evaluated after a 24-h p-CPnfs treatment in the G. mellonella larvae. Different concentrations of p-CPnfs (100, 500, 1000, 2000, 6000 ppm) were cautiously force-fed to the fourth instar larvae through the mouth of the insect by means of a micro-fine insulin syringe without causing any physical damage. 1000, 2000, and 6000 ppm of p-CPnfs significantly increased the total hemocyte counts (THCs) of the G. mellonella larvae. 500, 1000, 2000, and 6000 ppm of p-CPnfs increased the SOD activity of the larvae. 1000, 2000, and 6000 ppm of p-CPnfs increased the CAT activity in the hemolymph of the larvae. Unlike the results seen in SOD and CAT enzyme activities, all concentrations of p-CPnfs decreased AChE activity in the larval hemolymph. In addition to these results, LC50 value was found to be 8410 ppm for the force-fed larvae at the end of the 24-h period. Graphical abstract: [Figure not available: see fulltext.].