Diverse commercially available feeds are used in animal studies according to the purpose of the studies. We sought to understand the relationship between feed ingredients and their effects on animal physiology and behaviors. Here, we investigated how male laboratory mice (C57BL/6J ("B6") mice) were affected by chronic feeding with two commercially available diets, a non-purified diet (MF) and a semi-purified diet (AIN-93G). In B6 mice, both diets similarly induced spontaneous activities in the home cage and the open field box, anxiety in the elevated plus maze test, and depressive-like behaviors in tail-suspension and forced-swimming tests, and with both diets, similar data were obtained on calorie intake, water intake, body weight gain, and plasma corticosterone levels. By contrast, liver weight was significantly higher in MF-fed B6 mice than in AIN-93G-fed B6 mice. Furthermore, the cecum microbiome was drastically affected by the diets, and, specifically, Allobaculum was the major genus (43.4%) in the cecum microbiota of AIN-93G-fed mice but its abundance was reduced (to 3.8%) in the case of MF-fed mice. Future studies should address whether the differences in diet purity and cecum microbiota influence brain functions and behaviors in B6 mice.