Aims We tested extracts from Alpinia katsumadai seeds for anti-Campylobacter activity and investigated the roles of the CmeABC and CmeDEF efflux pumps in Campylobacter resistance to these natural phenolics. Additionally, we investigated an A.katsumadai ethanolic extract (AlpE) and other plant extracts as putative efflux pump inhibitors on Campylobacter isolates and mutants in efflux pump genes. Methods and Results AlpE showed antimicrobial activity against sensitive and multidrug-resistant Campylobacter isolates. CmeB inactivation resulted in the greatest reduction in resistance, while cmeF and cmeR mutations produced only moderate effects on minimal inhibitory concentrations (MICs). The chemical efflux pump inhibitors additionally reduced MICs in isolates and mutants, confirming that active efflux is an important mechanism in resistance to AlpE, with additional contributions of other efflux systems. A notable decrease in resistance to tested antimicrobials in the presence of subinhibitory concentrations of AlpE confirms its modifying activity in Campylobacter spp. Conclusions AlpE is important anti-Campylobacter source of antimicrobial compounds with resistance-modifying activity. At least two of the efflux systems are involved in the resistance to A.katsumadai antimicrobial seed extracts. Significance and Impact of the Study This is the first report of antimicrobial and resistance-modifying activity of AlpE from A.katsumadai seeds, demonstrating its potential in the control of Campylobacter in the food chain.