This research aims to determine whether cholecalciferol and taurine supplements may improve the efficacy of metformin in treating diabetic renal disease and reduce the risk of related complications. Materials and methods: the presented study was based on six distinct categories of rats, each consisting of six rats. Group I consisted of normal control rats (N); Group II contained diabetic control rats (D); Group III included diabetic rats treated orally with metformin. Group IV (Cho+M) consisted of diabetic rats that received a daily oral dosage of cholecalciferol plus metformin. Group V (TA+M) included diabetic rats treated with taurine in combination with a daily oral dose of metformin. Group VI involved diabetic rats that received a daily oral dosage of taurine, cholecalciferol, and metformin (Cho+TA+M). After six weeks, biological samples of blood and kidney tissues were gathered for biochemical, inflammatory markers levels and histological changes. Results: diabetic rats had elevated serum urea and interferon-gamma (INF-γ) levels, as well as reduced interleukin 10 (IL-10) levels in comparison to the normal control group. Additionally, several kidney histological alterations were noted in comparison to the normal control group. Combining cholecalciferol and taurine with metformin effectively improved all abnormal measurements. Cholecalciferol and taurine supplementation, along with metformin, may reduce diabetic kidney damage severity by leveraging their strong antioxidant, anti-inflammatory, and anti-apoptotic characteristics.