Escherichia coli were cultured in vitro to observe the effect of cadmium on bacterial growth as well as the adsorption of cadmium by rice bran insoluble dietary fiber (RBIDF) to investigate the protective effects of RBIDF on mice under chronic cadmium exposure. Mice were divided into the negative and positive control groups and RBIDF treatment group. After 8 weeks of feeding, cadmium levels in tissues, blood, and feces as well as fecal short chain fatty acids (SCFAs) were tested. DNA was extracted from intestinal flora in feces for high-throughput sequencing and fluorescence quantitative PCR detection. The results of the experiments showed that RBIDF can adsorb cadmium and protect the growth of E. coli. Cadmium content in blood, liver, small intestine, and feces of mice treated with RBIDF decreased by 66.67%, 57.67%, 27.15%, and 60.64%, respectively, when compared with that in the positive control group. The levels of the three types of SCFAs in feces increased by 1.30 times, 2.25 times, and 2.75 times, respectively. The total amount of intestinal bacteria in the RBIDF treatment group increased by 1.40 times. In addition, at the phylum level, the distribution of intestinal flora of the RBIDF treatment group was similar to that of the negative control group and was dominated by Bacteroidetes (68.75%), Firmicutes (23.67%), and Proteobacteria (6.82%). The positive control group was dominated by Bacteroidetes (55.71%), Firmicutes (33.25%), and Verrucomicrobia (5.62%). The results of this study suggest that RBIDF is able to adsorb cadmium to reduce cadmium concentration in the tissues and blood of mice, promote the recovery of intestinal flora in mice, and has a protective effect on chronic cadmium-exposed mice.