In the present study, the hybrid nanoflower PON1-Ca2+ (hNF-PON1) structure was synthesized and characterized and some antilipid drugs effects were investigated on hybrid paraoxonase (PON1) activity. Firstly, the hPON1 enzyme was purified 304.5 fold with 76.4% yield from human serum using the triple phase separation technique (TPP). Then, the hNF-PON1 was prepared in a one-step procedure using biomimetic mineralization. The catalytic activity of the hybrid enzyme with an 88.49% binding rate increased by 26.40%. The characterization of hNF-PON1 structure was performed with SEM, TEM, EDX, FT-IR and XRD analyzes. The effects of some lipid-lowering drugs (Valeric acid, phenoxy – isobutyric acid, N-desmethyl rosuvastatin) were also investigated on the activity of hNF-PON1 enzyme. When the re-usability of the enzyme was tested 10 times in succession, the enzyme was determined to protect the activity by 60%. Inhibition kinetics (IC50 and Ki values) of hybrid structure was determined. In the last stage of the study, the potential toxic effect of hNF-PON1 structure was evaluated using zebrafish embryos. To this end, zebrafish embryos were exposed to hNF-PON1 with 50-2000 ppm concentrations and monitored at 24, 48, 72 and 96 hpf. Survival rate, hatching rate and body malformations were evaluated during this period and it was determined that the hNF-PON1 structure did not exhibit any toxicity on zebrafish embryos.