Objective To analyze the effect of Calcitriol combined with Sitagliptin in the treatment of patients with type 2 diabetic nephropathy on bone metabolism and creatinine (SCr), β2 microglobulin (β2-MG), blood urea nitrogen (BUN), albumin (ALB), 24 h urinary protein quantification (24 h UTP) and urinary microalbumin/creatinine ratio (ACR). Methods According to the random number table method, 96 patients with type 2 diabetic nephropathy who were admitted to Southern Medical University Nanfang Hospital Baiyun Branch from January to October 2021 were divided into two groups, with 48 cases in each group. After admission, the patients were given routine antihypertensive, health education, diet and exercise guidance and other treatments, the patients in the control group were treated with Sitagliptin on the basis of conventional treatment, and the patients in the observation group were treated with Calcitriol on the basis of the control group, both groups were treated for 1 month. The clinical efficacy of the two groups of patients after treatment, SCr, β2-MG, BUN, ALB, 24 h UTP, ACR, bone mineral density, serum calcium (Ca), serum phosphorus (P), intact parathyroid hormone (iPTH), bone growth protein (BGP) levels before and after treatment, and occurrence of adverse reactions during treatment were compared. Results After treatment, the total effective rate of patients in the observation group was higher than that in the control group; the total incidence of adverse reactions during the treatment period was lower than that in the control group, but there was no significant difference after comparison (all P >0.05); after treatment, the bone mineral density, Ca, P and ALB levels of the two group significantly increased, and the observation group was significantly higher than the control group; iPTH, BGP, BUN, β2-MG, 24 h UTP levels significantly decreased, and the observation group was significantly lower than the control group (all P <0.05). Conclusion Calcitriol combined with Sitagliptin in the treatment of type 2 diabetic nephropathy can improve clinical therapeutic effect, improve bone metabolism and renal function, and has good safety.