Inflammatory skin diseases such as psoriasis and atopic dermatitis represent a significant and ever-increasing health burden globally. Conventional steroid therapies are ill-suited for long-term continuous usage as they are accompanied by adverse effects. While biologics such as monoclonal antibodies are highly effective in severe disease, they are not prescribed in the vast majority of mild-moderate cases and are largely inaccessible due to their high cost. RP23 is a modified human self-peptide with novel anti-inflammatory properties. Topical formulations of this peptide effectively treat both imiquimod-induced psoriasis and oxazolone-induced atopic dermatitis models in mice. Unlike steroids which have systemic effects, RP23 only suppresses local immune responses where it is needed. Importantly, RP23 is well tolerated by mice with no adverse events unlike steroids which reduced body weight and caused skin atrophy. Using fluorophore conjugated RP23, we determined that the peptide is primarily taken up by neutrophils, macrophages, and dendritic cells. Confocal microscopy of murine bone marrow-derived macrophages (BMDM) also demonstrated that RP23 was readily taken up by these cells and co-localised with lysosomes, consistent with phagocytosis. In-vitro BMDM assays, as well as studies in human monocyte-derived macrophages, demonstrated that RP23 reduced IL-6 and IL-12p40 release, which likely explains its mechanism of action in these diseases. Thus, RP23 represents a promising new therapeutic for inflammatory skin diseases. It enjoys many clinical advantages over existing therapeutics, including being a cheaper, convenient, safer, and potentially more effective treatment option for psoriasis and atopic dermatitis.