Despite recent scientific advancement and globalization, the system of traditional medicine and complementary/alternative medicine is considered as a primary health care modality in the resource-constrained health care settings. Traditional antibiotics are increasingly suffering from the emergence of efflux related multidrug resistance (MDR) amongst pathogenic bacteria that led to novel approaches to control microbial infections being investigated as potential alternative treatments. Synergism between natural sources and antibiotics has received much attention and efforts have been put in to identify plant extract that can act as an efflux pump inhibitor. The mode of action of combination therapy significantly differs from that of the same drugs when used alone. Efflux related MDR such as AcrAB-TolC in S. typhimurium is a significant way of escaping from the effects of selected antimicrobial agents. EPI activity was done by berberine uptake and Ethidium bromide accumulation assays. The target of EPI strategy is to block the efflux pumps so that the concentration of antibiotics may increase in the bacterial cells and they can easily access their target site.