Background and objectives: Psoriasis is a prevalent, chronic, and inflammatory disorder with good response rates using novel treatment strategies. However, side effects are a limiting factor in long-time treatment. Recent studies have demonstrated that many natural remedies have fewer side effects, and are thus safer options. The aim of this study was to evaluate the efficacy of a novel topical herbal preparation in patients with plaque psoriasis. Methods: This randomized, triple-blind, vehicle-controlled, two-arm parallel trial was conducted in patients with mild-to-moderate plaque psoriasis (psoriasis area & severity index= PASI score< 12). We randomized 108 patients in 1:1 ratio to receive Boswellia-based cream (containing Boswellia spp. ethanolic extract, Boswellia spp. oil, Glycyrrhiza glabra extract, Cucurbita pepo pulp oil) or vehicle cream, both applied as a thin layer on skin lesions twice daily for four weeks. Results: Compared with vehicle, the Boswellia-based cream group showed greater reduction in mean PASI score from baseline to week two and from week two to week four (both p