Protein engineering-based drug designing is quite interesting research area for invention of peptide based drugs. The current study is aimed to engineer BuforinII antimicrobial peptide by Mechanism based protein engineering. Template BuforinII was obtained from NCBI database and its similar sequences were retrieved by using Blast P. Protein engineering resulted in a total of 200 variable peptides. 3D model developed for 200 variable peptides and BuforinII by using PEPFOLD server. The developed models were evaluated by RAMPAGE and Q-Mean servers. Based on the Ramachandran Plot, Z-score value and SVM-score of DNA binding studies, the P11A/V12P variant was found to be highly stable and more DNA binding compared with wild and remaining variants. The developed variants can be used for antimicrobial studies in laboratory.