ABSTRACT Introduction: Oleuropein is a promising nutraceutical found in abundance in olive leaf, with reported antioxidant and anti-inflammatory properties, and hence could be a valuable treatment for dermatological diseases such as psoriasis. Areas covered: In order to overcome the poor skin penetration of oleuropein, it was formulated in a microemulsion nanocarrier. The selected microemulsion formulation displayed a particle size of 30.25 ± 4.8 nm, zeta potential 0.15 ± 0.08 mV and polydispersity index 0.3 ± 0.08, with storage stability for 1 year in room temperature and total deposition in skin layers amounting to 95.67%. Upon clinical examination in psoriatic patients, the oleuropein microemulsion formulation was proven superior to the marketed Dermovate cream composed of clobetasol propionate, in terms of reduction of Psoriasis Area and Severity Index (PASI) scores, as well dermoscopic imaging and morphometric analysis of the psoriasis lesions, in which oleuropein microemulsion exhibited marked improvement in the clinical manifestations of psoriasis. Expert opinion: The findings of this study further prove the promising role of nutraceuticals, as well as nanoparticles in enhancing the therapeutic outcome of treatments, and open new era of applications in a variety of diseases.