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Aims: The current study aims to create a formulation of Fluvastatin sodium (FVS) loaded niosome for the treatment of antihyperlipidemia using thin film hydration. The developed formulations were statistically optimized by two factors, three levels by 3-level factorial design and were evaluated for vesicle size, entrapment efficiency, zeta potential, transmission electron microscopy, and in-vitro drug release. Methods: The optimized FVS niosome being transformed to gel formulation was likewise analyzed for in-vitro skin permeability study, lipase action, and stability study. Results: The composition of an improved FVS niosome revealed vesicle size, entrapment effectiveness, zeta potential of 105.3 ± 12.4nm, 74.5 ± 0.86% and -36.2 ± 7mV, respectively, with spherical morphology. Conclusion: The FVS Niosomal gel demonstrated improved skin permeation compared to Orlistat. Furthermore, lipase activity showed better activity when compared with standard Orlistat drugs. Niosomal particles were discovered as a reliable nanovesicular carrier for the transdermal administration of FVS.