Inflammatory skin diseases such as psoriasis, which affect up to 4% of the Western population, can be highly debilitating. Current therapies are not always efficacious, are costly and have adverse effects. New therapies that provide cost-effective and targeted suppression of inflammation are needed. We have uncovered a novel role for a human peptide in modulating and suppressing inflammation. A version of this peptide (called RP23) was chemically synthesised with modifications to enhance ease of production and allow tagging to track the peptide in immunological studies. Culture of primary human or murine macrophages with RP23 led to reduced IL-12/23(p40) and IL-6 release after TLR-stimulation. When injected intra-dermally into human skin explants, RP23 reduced activation of dermal dendritic cells. In a mouse model of contact dermatitis, a single RP23 injection prior to sensitisation significantly suppressed elicitation of inflammation. Further, in a murine model of imiquimod-induced psoriasis, RP23 reduced erythema, skin thickness and scaling, reduced T-cells in psoriatic skin and increased the proportion of FoxP3+CD4+ T-cells in local skin draining lymph nodes. When applied topically, RP23 penetrated the stratum corneum and colocalised with cells in murine and human skin explants. Importantly, topical RP23 suppressed psoriasis in mice when given either prophylactically or therapeutically. Topical RP23 also reduced severity of a murine model of atopic dermatitis. The effects were isolated to the local area in which RP23 was delivered, unlike conventional therapies which caused systemic immune suppression. RP23 therefore represents a novel, locally acting peptide-based therapy that could improve management of inflammatory skin diseases.