Recent findings highlight the role of skin microbiome in modulating immune function and inflammatory response. This systematic review aims to investigate the effects of muds, already used for the treatment of several rheumatic and dermatologic conditions, on skin microbiome. Medline via PubMed, Embase, Cochrane Library, and Google Scholar were searched for articles about the effects of therapeutic muds on microorganisms of skin microbiome. Five studies were included in the review and critically appraised. Limited data suggest that muds have various properties that may explain their action on skin microbiome, with different effects on commensal and pathogenic microorganisms. Further investigation on this topic is needed to better characterize the effects of different muds on skin microbiome, thus possibly extending their indications.