We explored the effects of dietary supplementation with phlorizin on redox state-related gut microbiota homeostasis in an obesity mouse model. Mice (C57BL/6J) were grouped as follows for 12 weeks: normal chow diet group (NCD), high-fat and cholesterol diet group (HFD), and treatment groups fed with HFD along with three levels of phlorizin. Phlorizin alleviated the hyperlipidemia and redox status and increased the total ccal SCFA content (1.88 ± 0.25 mg/g). Additionally, phlorizin regulated gene expression related to lipid metabolism, redox status, and cecum barrier and rebuilt gut microbiota homeostasis. After interference by antibiotics, the total phloretin content in the feces was decreased about 4-fold, and most of the health-promoting effects were abolished, indicating that phlorizin might be susceptible to microbial biotransformation and that microecology is indispensable for maintaining the redox state capacities of phlorizin. Phlorizin treatment could be an advantageous option for improving HFD-related obesity and redox states related to gut microbiota homeostasis.