Background: The study was conducted to evaluate the protective effects of Spironolactone (25mg OD) along with Ramipril (5mg) on diabetics (30-70yr) in relation to proteinuria and state of Diabetic Nephropathy. Material and Methods: A comparative, prospective, non-randomized, non-blinded experimental study was conducted on 32 patients (30-70yr) of diagnosed Type 2 Diabetes Mellitus showing proteinuria. Total duration of study was about one year from October 2017 to October 2018. Subjects were followed over 12 weeks and baseline and 12-week Urine ACR being compared. Initially there were total 32 patients out of which 4 patients did not came for follow up, hence total 28 patients were included in the study. Base line Urine ACR values were compared with follow up Urine ACR values at 12 weeks. Other base line laboratory investigation such as serum lipid profile, HbA1c, eGFR, fundus examination, ultrasonography (KUB), serum urea, serum creatinine, haemoglobin, were taken at the starting point. Results: Patients after receiving drug (spironolactone 25mg along with Ramipril 5mg) were followed for 3-month duration and response were assessed by measuring urine ACR value at end of 3 months. Mean values of baseline and follow up Urine ACR for Group was 471.5±465.62, 244.66±237.54 respectively. For comparing effects, paired t test was applied,t calculated was found more that value of t observed with p value <0.05 which proved statistically significant and denotes that there was significant reduction of proteinuria over 12 weeks follow up period in. It was observed that percentage reduction of Urine ACR was 48%. Conclusions: In the study it was concluded that combination of spironolactone and ramipril had significant effect over proteinuria reduction over follow up period in patient with diabetic nephropathy. Significant reduction of proteinuria occurred over 12 weeks follow up period 48%.