A very important disease of younger age that usually appears and leads to death of neonate in case of improper diagnosis and treatment is Neonatal calf diarrhea. Disease has its own economic importance as livestock has a major role in gross domestic production (GDP) of Pakistan. A trail was conducted to check chemo-prophylactic effects of different anti-diarrheal drugs. Thirty neonates were selected and divided into six equal groups treated respectively with Colimune Ora, Cosumix Plus, Streptomegma, NMK Powder and Biovet by keeping last group as control. Blood sample were collected to check any untoward change in blood just after birth, on 3rd and 28th day of experiment. Mixed results were found in hematology on 28th day with overall increasing pattern in Total leukocyte count (TLC) and Packed cell volume (PCV). IN contras Total erythrocyte count (TEC) shows increase of 16.57%, 96% and 93.47% respectively in case of Colimune Ora, NMK and Cosumix Plus whereas decrease in case of Streptomegma and Bio Vet up-to 5.06%. Mixed results concerning DLC, serum sodium and potassium level were witnessed. Inclusively there was no annoying change was noticed with increase in (TLC) eventually providing protection to animal to avoid the disease. Henceforward use of above listed drugs prophylactically especially Cosumix Plus, strongly suggested against neonatal calf diarrhea to lessen the mortality due to neonatal calf diarrhea.