With increased global warming, the impact of high temperature and humidity (HTH) on human health is increasing. Traditional Chinese medicine describes the Herb Yinchen as a remedy for reducing heat and eliminating dampness. This study focused on the impact of HTH conditions on mice and the potential protective effect of Herb Yinchen. Five male Balb/c mouse groups included two normal control groups, two HTH-exposed groups, and one Yinchen-treated group. For either three or ten days, normal and HTH-exposed mice were housed under normal or HTH (33 ± 2 °C,85% relative humidity) conditions, respectively. Yinchen-treated mice, housed under HTH conditions, received the Herb Yinchen decoction for three days. Metabolite profiles of plasma and liver samples from each group were analyzed using LC-MS/MS. Fecal DNA was extracted for 16S rDNA analysis to evaluate the intestinal microbiome. Spearman correlation analysis was performed on metabolites, bacteria, and bile acids that differed between the groups. We found that HTH altered the host metabolite profiles and reduced microbial diversity, causing intestinal microbiome imbalance. Interestingly, Herb Yinchen treatment improved HTH-mediated changes of the metabolite profiles and the intestinal microbiome, restoring them to values observed in normal controls. In conclusion, our study reveals that HTH causes intestinal bacterial disturbances and metabolic disorders in normal mice, while Herb Yinchen could afford protection against such changes.