Colistin remains a last-line antibiotic against multidrug-resistant Gram-negative pathogens, but its clinical utility is limited by nephrotoxicity and emerging resistance. This study identifies macelignan, a natural lignan from nutmeg, as a potent synergist that enhances colistin activity against IMPORTANCE: The continued efficacy of colistin, a last-line antibiotic against multidrug-resistant Gram-negative pathogens, is increasingly threatened by dose-limiting nephrotoxicity and the global spread of resistance determinants. This study introduces macelignan-a naturally occurring lignan from nutmeg-as a highly effective colistin adjuvant that operates through a previously unrecognized mechanism centered on metabolic disruption. By targeting the bacterial citric acid cycle, macelignan depletes intracellular ATP, thereby crippling the energy-dependent machinery required for membrane repair following colistin-induced damage. This dual "internal and external pincer" strategy not only dramatically reduces the colistin concentration needed for bactericidal activity but also significantly lowers bacterial burden