Background The alarming occurrence of renal failure in both old and young in this environment has been credited mainly to hypertensive nephrosclerosis and diabetic nephropathy. At the early stages, the renal insufficiency, caused by these disease conditions can be arrested or deterred. Until now, serum creatinine/creatinine clearance has been the analyte of choice in the assessment of renal function. Recent findings have suggested that cystatin C is a better marker of the GFR and renal function, compared to the widely used plasma creatinine. This study therefore aimed at assessing the GFR of newly diagnosed hypertensives and diabetics using plasma cystatin C. Methods This was a case-controlled study made up of forty consecutive patients (twenty hypertensives and twenty diabetics, patients who had both were excluded), and forty apparently healthy age- matched controls. Plasma cystatin C and plasma creatinine were measured in the eighty respondents and their GFR was estimated using the Cockcroft and Gault’s algorithm. Statistical package for social sciences (SPSS) was used in the statistical analyses. Results While plasma cystatin C and plasma creatinine correlated significantly with the estimated GFR, the area under the curve of plasma cystatin C was greater than that of plasma creatinine in an ROC plot. Linear regression also revealed that the concentration of plasma cystatin C and its reciprocal were more informative in the groups with normal and mildly reduced GFR, while only plasma creatinine predicted the estimated GFR in the group with moderately reduced GFR. Conclusions Both plasma cystatin C and plasma creatinine are good predictors of the GFR but plasma cystatin C is a better predictor and earlier indicator of early reductions in GFR and renal functions. This will be of immense value in the management of these conditions.