The search for Antimicrobial agents has been carried out for decades due to its importance in bacterial diseases. Antimicrobial activity of benzimidazole type of Fluconazole analogues series were subjected to Quantitative Structure Activity Relationship (QSAR) Analysis with an effort to derive and understand a correlation between the biological activity as response variable and different molecular descriptors as independent variables. The 2D technique indicates the importance of SsOHcount, HUMO energy, SsBrE-index, SssOE-index and Alignment independent T_N_F_1, T_2_Cl_1 of the compounds on the activity. The QSAR results revealed that the presence of methoxy, hydroxy, chloro or fluoro substituents would increase the antimicrobial activity and presence of electron withdrawing groups at R1, R2, R3 and R4 position of benzimidazole ring would increase the activity. The study suggests that benzimidazole may be acting as an antimicrobial compound and may be therefore included in the category of leads for bacterial infection.