Titanium dioxide nanoparticles (TiO2 NPs) are generally added in considerable amounts to food as a food additive. Oral exposure to TiO2 NPs could induce intestinal damage, especially in obese individuals with a high-fat diet. The probiotic Bacillus coagulans (B. coagulans) exhibits good resistance in the gastrointestinal system and is beneficial to intestinal health. In this study, B. coagulans was used to treat intestinal damage caused by TiO2 NPs in high-fat-diet mice via two intervention methods: administration of TiO2 NPs and B. coagulans simultaneously and administration of TiO2 NPs followed by that of B. coagulans. The intervention with B. coagulans was found to reduce the inflammatory response and oxidative stress. A 16S rDNA sequencing analysis revealed that B. coagulans had increased the diversity of gut microbiota and optimized the composition of gut microbiota. Fecal metabolomics analysis indicated that B. coagulans had restored the homeostasis of sphingolipids and amino acid metabolism. The intervention strategy of administering TiO2 NPs followed by B. coagulans was found to be more effective. In conclusion, B. coagulans could alleviate intestinal damage induced by TiO2 NPs in high-fat-diet mice TiO2B. coagulans. Our results suggest a new avenue for interventions against intestinal damage induced by TiO2 NPs.