Abstract Here 6 (H)-1, 3, 4-thiadiazine analogues have been used to correlate the inhibiting constant with the eccentric connectivity index (ECI), fragment complexity (FC), McGowan volume (MG) and topological polar surface area (TPSA) for studying the quantitative structure activity relationship (QSAR). Correlation may be an adequate predictive model which can help to provide guidance in designing and subsequently yielding greatly specific compounds that may have reduced side effects and improved pharmacological activities. The literature survey revealed that there are so many models available for MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9 and MMP-13, but QSAR model in respect of MMP-12 inhibition was necessity. We have used multiple linear regression (MLR) for developing QSAR model. For the validation of the developed QSAR model, statistical analysis such as cross validation test, standard deviation, quality factor, fischers test, root mean square deviation (RMSD), variance; and internal validation such as Y-randomization test have been performed and all the tests validated this QSAR model with fraction of variance r2= 0.9364 and LOO-CV variance q2= 0.9146. Thirteen novel 6 (H)-1, 3, 4-thiadiazine analogues have been designed and their inhibiting constant have been calculated with the developed QSAR model. It was found that the calculated inhibiting constant of these analogues were within the same range as of the training set. Further, these 6 (H)-1, 3, 4-thiadiazine analogues have been docked with the catalytic domain of human matrix metalloproteinase (MMP12) which shows better docking score as compared to the (N-hydroxy-2-(N-hydroxyethyl) biphenyl-4-ylsulfonamido) acetamide, a MMP12 inhibitor. The results suggested that the designed novel 6 (H)-1, 3, 4-thiadiazine analogues could be developed as a good MMP12 inhibitors.