Diabetic kidney disease (DKD) is a prevailing complication arising from diabetes mellitus. Unfortunately, there are no trustworthy and efficacious treatment modalities currently available. In recent times, compelling evidence has emerged regarding the intricate correlation between the kidney and the gut microbiota, which is considered the largest immune organ within the human physique. Various investigations have demonstrated that the perturbation of the gut microbiota and its associated metabolites potentially underlie the etiology and progression of DKD. This phenomenon may transpire through perturbation of both the innate and the adaptive immunity, leading to a burdensome allostatic load on the body and ultimately culminating in the development of DKD. Within this literature review, we aim to delve into the intricate interplay between the gut microbiota, its metabolites, and the immune system in the context of DKD. Furthermore, we strive to explore and elucidate potential chemical interventions that could hold promise for the treatment of DKD, thereby offering invaluable insights and directions for future research endeavors.