Psoriasis is a complex immune-mediated disease that has been closely associated with obesity and lipid metabolism disorders. This study investigated the effects of hydrogen-rich water (HRW) on imiquimod-induced psoriasis-like skin inflammation in ApoE-deficient mice. Psoriasis severity as well as the lipid levels and inflammatory markers were evaluated. The results revealed that HRW significantly reduced plasma triglyceride and total cholesterol levels, increased high-density lipoprotein cholesterol levels, and alleviated skin lesions in mice. Transcriptomic data of the skin tissues indicated significant changes in the inflammatory and lipid metabolism pathways after HRW treatment and quantitative PCR validated the regulation of inflammatory cytokine expression. In addition, HRW promoted M2 macrophage polarization and reduced M1 macrophage polarization in the skin. These results suggest that the consumption of HRW may be a potential therapeutic strategy for psoriasis accompanied by abnormal lipid metabolism.