Management for psoriasis, a chronic inflammatory skin disease, is complicated. The goal is to investigate how luteolin-loaded liposomes might be used to create a novel psoriasis treatment strategy. In this current research, luteolin loaded liposomes (LLL) were prepared by using ether injection method. The formulation was characterized with UV-Visible spectroscopy, ATR-FTIR, DSC, measurement of particle size, zeta potential, and poly dispersity index. Moreover, wavelength at absorbance maxima (λ-max) of luteolin in a phosphate buffer solution with pH value 7.4 was determined. The in vivo anti-psoriatic activity was determined in a mouse tail model. The development of a calibration curve made direct measurement in UV-Vis possible. The presence of groups such as carboxyl, amine, esters, hydroxyl, nitrile, and nitro were determined in the ATR-FTIR. DSC is indeed used to evaluate the interactions and thermal stability of the compounds. In this current study, in the characterization of liposomes the particle size has a great impact. The optimal zeta potential of -20.8 mV is because of dissociation of carboxylic acid groups on the surface of cholesterol nanoparticles and it varies depending on the formulation. If nanoparticles are homogeneous, the polydispersity index (PDI) will be typically less than 0.351. In in vivo model for psoriasis, topical application of LLL resulted in significant reduction of psoriatic symptoms such as scaling, redness, and overall disease severity. The results demonstrate the potential of LLL for the management of psoriasis.