The aim of the present research work is to formulate lacidipine (LAC) loaded niosomes formulation for the management of hypertension by thin film hydration technique. The developed formulations were statistically optimized by four factors, three levels Box-Behnken design and were evaluated for vesicle size, entrapment efficiency, and flux. The optimized LAC niosomes was further evaluated for permeation depth by confocal laser scanning microscopy (CLSM) and converted to gel formulation. Further, the optimized LAC niosomes gel was evaluated for ex-vivo permeation study, skin irritation study, stability study and pharmacodynamics study. The optimized LAC niosomes formulation showed vesicle size, entrapment efficiency and flux value of 676.98±10.92nm, 82.77±4.34% and 38.43±2.43μg/cm/h respectively, with spherical morphology. The comparative CLSM study showed that optimized LAC niosomes formulation has shown maximum permeation (70.75μm) as compare to LAC liposomes formulation (58.26μm). The optimized LAC niosomes gel showed skin permeation enhancement of 2.15 times as compare to control gel. Furthermore, in vivo antihypertensive activity showed significantly higher (p<0.001) reduction in blood pressure compared to oral suspension. Indeed, it was found that niosomal vesicles represented to be an efficient nano vesicular carrier for transdermal delivery of lacidipine.