The present study evaluates the cystatin C, glomerular filteration rate (GFR) and vanillylmandelic acid (VMA) in comorbid diabetic and hypertensive patients attending Federal University Teaching Hospital, Owerri, Nigeria. A total number of 200 persons were recruited for the research; 50 controls, 50 hypertensive, 50diabetic, and 50 hypertensive-diabetic persons. The respondents were Federal Teaching Hospital, Owerri. Verbal consent was sort and questionnaires were used to extract information regarding biodata and patients’ history of diabetes and hypertension. Blood pressure was determined. A standard venepuncture method was used to obtain seven milliliters (7ml) of blood from all the subjects under asceptic conditions. 3milliliters was dispensed into a plain container capped, labeled appropriately and allowed to clot at room temperature. The serum were separated from the red cell by spinning at 4,000 r.p.m for 5minutes. The supernatant serum obtained were stored frozen at -20 0C until the day of analysis. The remaining 2ml of blood was dispensed into a fluoride oxalate container for the estimation of fasting blood glucose. 5ml of urine was collected into sterile universal bottle, then aliquot into cryovials and stored at -20oC till the day of assay. All reagents were commercially purchased and the manufacturer’s standard operating procedures was strictly adhered to. The fasting blood sugar levels was higher in diabetic-hypertensive group (199.50  25.36 mg/dl) and diabetic groups (209.85  19.95 mg/dl) compared to hypertensive (84.10  9.03 mg/dl) and control group (84.20  9.40 mg/dl). The mean value of the diastolic pressure of the diabetic-hypertensive group (102.90  6.87 mmHg) decreased which was statistically significant (P<0.05) when compared with the diabetic group (75.10  4.58 mmHg). The mean value of the systolic pressure of the diabetic-hypertensive group (160.00  7.36 mmHg) was decreased which was statistically significant (P<0.05) when compared with the diabetic group (115.30  6.14 mmHg). Serum creatinine increased in diabetic-hypertensive group when compared with other groups. The cystatin C levels was higher in hypertensive group (0.90  0.14 mg/l) and lower in diabetic-hypertensive group (0.84  0.17 mg/l) but the mean difference between the groups was not significant (P >0.05). The mean value of VMA was higher in diabetic-hypertensive group (12.48  2.25 mg/24hr) compared to diabetic (11.26  1.74 mg/24hr) and control (9.96 1.43 mg/24hr) group. There was decrease in the mean value of GFR of diabetic-hypertensive group (71.80  8.30 ml/min/1.73m2) which was not statistically significant (P>0.05) when compared with other groups. While there was an increase in GFR value of hypertensive group when compared with other groups. There was a positive correlation between creatinine and cystatin C (r = 0.337) and their association was significant (p<0.05). There was a negative correlation between creatinine and VMA (r = -0.164) and their association was significant (p<0.05). There was a negative correlation between creatinine and GFR (r = -0.558) and their association was significant (p<0.05). There was a negative correlation between cystatin C and VMA (r = -0.078) and their association was not significant (p>0.05). There was a positive correlation between cystatin C and GFR (r = 0.019) and their association was not significant (p>0.05). In conclusion, good control of blood glucose and blood pressure level reduces the likelihood of the development of renal impairment which is usually associated with both diabetes and hypertension. Co-morbidity of diabetes and hypertension poses a higher risk of developing renal disease. Both serum creatinine, cystatic C and GFR are important biomarkers for renal impairment hence should be monitored on a regular basis for diabetic and hypertensive patients and much more frequently for hypertensive-diabetic patients.