A set of twenty-one compounds Furanones derivatives with anti-bacterial activity was subjected to the two dimensional quantitative structure activity relationships studies using V life molecular drug design suit. Drug Designing module describe with various combinations of molecular connectivity indices, electro topological indices, alignment independent descriptors and other 2D descriptors. Furanones derivatives was taken as the lead molecule and QSAR model developed using multiple regression approach. For each set of descriptors, the best multi-linear QSAR equations were obtained by the stepwise variable selection method using leave-one-out cross-validation as selection criterion. Logarithmic inverse value of IC50 was taken as dependent variable and electro topological descriptor (SdOE-index and SsCH3E-index) was taken as independent variable. The best QSAR model (r2 = 0.7614, F = 20.73, r2 se = 0.36, q2 se = 0.4248, Pred_r2 = 0.5038, pred_r2se = 0.3595) has acceptable statistical quality and predictive potential as indicated by the value of cross validated squared correlation coefficient (q2 = 0.679. Thus this validated model brings important structural insight to aid the design of novel anti-bacterial activity.