Objectives Diabetic nephropathy (DN) is one of the most common and serious complications of diabetes. The purpose of this study was to explore the relationship between serum microRNA-338-3p (miR-338-3p) and miR-105-3p and bone metabolic markers in patients with DN at different stages. Methods A total of 153 patients diagnosed and treated in the Department of Nephrology from July 2020 to October 2021 were selected as the study objects. According to the staging criteria of diabetic nephropathy and 24-h urinary albumin quantitative level, the patients were divided into control group (35 cases), microalbuminuria group (37 cases), clinical stage albuminuria group (27 cases) and renal failure group (54 cases). Gene expressions were measured by real-time fluorescence quantitative PCR. The correlation was analyzed by Spearman. Serum miR-338-3p and miR-150-5p in the prediction of renal failure in DN was analyzed by ROC curve. Results The levels of urinary albumin and serum creatinine were markedly increased with the increase of DN stage (p < 0.05). Compared with the microalbuminuria group, the expression levels of serum miR-383-3p, serum miR-105-3p, 25(OH)-D, BGP and PINP were obviously decreased, but the expression of parathyroid hormone (PTH) and type I collagen (β-CTX) was largely increased in clinical proteinuria group (p < 0.05). Compared with the clinical proteinuria group, the expression levels of serum miR-383-3p, serum miR-105-3p, 25(OH)-D, BGP and PINP were largely decreased, but the expression of PTH and β-CTX was obviously increased in the renal failure group (p < 0.05). Spearman correlation results showed that serum expressions of miR-383-3p and miR-105-3p were negatively correlated with PTH and β-CTX, and positively correlated with 25(OH)-D, BGP and PINP (p < 0.05). ROC curve analysis showed that the AUC of serum miR-338-3p and miR-150-5p was 0.896 with the specificity and sensitivity of 96.66% and 73.47%, which had certain predictive value for the occurrence of renal failure in DN. Conclusions The expression levels of serum miR-383-3p and miR-105-3p were significantly correlated with bone metabolism markers. The combined test can provide new ideas and insights for the clinical treatment of osteoporosis in DN.