Correlation between the serum cystatin C and substance P in peripheral blood of diabetes mellitus patients complicated with hypertension was investigated. Diabetes mellitus patients with or without hypertension were selected in No. 215 Hospital of Shaanxi Nuclear Industry from December 2015 to February 2017. There were 60 patients with only hypertension (hypertension control group), 60 patients with only diabetes mellitus (diabetes mellitus control group) and 60 patients with diabetes mellitus combined with hypertension (observation group). Levels of serum cystatin C and substance P in peripheral blood were measured via immunoturbidimetry and enzyme-linked immunosorbent assay, respectively, and the correlation with hypertension was analyzed. The average level of serum cystatin C in the observation group was higher than that of the two control groups (P<0.05). The level of substance P in peripheral blood of the observation group was lower than that of the diabetic control group (P<0.05). The levels of serum cystatin C in patients with grade III hypertension in observation group were higher than those in grades II and I, and the levels of substance P in peripheral blood of patients with grade III hypertension in observation group were lower than those in grades II and I. Systolic pressure of patients in observation group was significantly positively correlated with level of serum cystatin C, but significantly negatively correlated with level of substance P in peripheral blood (P<0.05). Compared with the diabetes mellitus patients, level of serum cystatin C was higher, and level of substance P peripheral blood was lower in diabetes mellitus patients complicated with hypertension. In diabetes mellitus patients, blood pressure was positively correlated with serum cystatin C level, and negatively correlated with substance P level in peripheral blood.