Heavy metals released in the environment pose a huge threat to soil and water quality, food safety and public health. Additionally, humans and other mammals may also be directly exposed to heavy metals or exposed to heavy metals through the food chain, which seriously threatens the health of animals and humans. Chromium, especially hexavalent chromium [Cr (VI)], as a common heavy metal, has been shown to cause serious environmental pollution as well as intestinal damage. Thus, increasing research is devoted to finding drugs to mitigate the negative health effects of hexavalent chromium exposure. Seaweed polysaccharides have been demonstrated to have many pharmacological effects, but whether it can alleviate gut microbial dysbiosis caused by hexavalent chromium exposure has not been well characterized. Here, we hypothesized that seaweed polysaccharides could alleviate hexavalent chromium exposure-induced poor health in mice. Mice in Cr and seaweed polysaccharide treatment group was compulsively receive K2Cr2O7. At the end of the experiment, all mice were euthanized, and colon contents were collected for DNA sequencing analysis. Results showed that seaweed polysaccharide administration can restore the gut microbial dysbiosis and the reduction of gut microbial diversity caused by hexavalent chromium exposure in mice. Hexavalent chromium exposure also caused significant changes in the gut microbial composition of mice, including an increase in some pathogenic bacteria and a decrease in beneficial bacteria. However, seaweed polysaccharides administration could ameliorate the composition of gut microbiota. In conclusion, this study showed that seaweed polysaccharides can restore the negative effects of hexavalent chromium exposure in mice, including gut microbial dysbiosis. Meanwhile, this research also lays the foundation for the application of seaweed polysaccharides.