Abstract: The mechanism of hydrolysing the β-lactam antibiotics by β-lactamases is referred to as antibiotic resistance and this could be reduced by introducing some β-lactamase inhibitors. However, surprisingly these inhibitors also have the property to defend bacteria and therefore are used in combination with antibiotics which still gain resistance owing to the property of multi-drug resistance by the use of MRSA (Methicillin-resistant Staphylococcus aureus). Therefore, the present study was focused on the inhibitory activity of a set of natural compounds (Gallic acid, Propyl Gallate, Kaempferol, Quercetin, Mangostin and Rubraxanthone) from natural resources against β-lactamase in MRSA by insilico interaction studies using Autodock4 suite. Their corresponding interactions at the binding sites were studied after inducing the solvation properties. Before performing the hydrogen bond interactions the ligands were subjected to ADMEtoxicity (Absorption, distribution, Metabolism and Excretion) analysis and were further examined to find out the optimum pose of the ligands in order to choose the best among them. However, Kaempferol exhibited best interactions with minimum inhibitory constant and thus was selected as the best inhibitor for this study.