<p>This study aimed to improve the oral bioavailability and antihyperlipidemic activity of lovastatin (LT) by formulating piperine-coated nanostructured lipid carriers (NLCs). NLCs were prepared using ultrasonication method. The particle size and entrapment efficiency of the NLCs ranged from 131.22 to 358.46&#xa0;nm and 72.13 to 92.11%, respectively. The zeta potential of the NLCs was within the optimal range. Different concentrations of piperine were used to coat the NLCs to enhance intestinal permeation and bioavailability of LT. The results revealed that the presence of piperine in NLCs significantly improved intestinal permeation, with a permeability coefficient of 0.24 × 10^-6&#xa0;cm/s. The flux of PNL2 (piperine enabled NLCs) was found to be 3.12&#xa0;µg/cm² × h, demonstrating a higher permeation enhancement compared to NL6 and LT suspension. The relative bioavailability of PNL2 was found to be 4.7 times greater than that of the LT suspension and 1.5 times greater than that of the NL6 formulation. These bioavailability results were further supported by antihyperlipidemic studies, which showed superior efficacy of PNL2 compared with NL6. Based on these findings, it can be concluded that NL6 improved both bioavailability and antihyperlipidemic activity compared to the LT suspension, whereas PNL2 demonstrated even greater enhancements in both bioavailability and therapeutic efficacy.</p>