Polymyxin serves as the "last line of defense" for treating infection with multidrug-resistant Gram-ne-gative bacteria. However, the emergence and spread of polymyxin-resistant genes such as mcr-1 severely weakens its clinical efficacy. This paper systematically summarizes the antimicrobial and resistance mechanisms of polymy-xin, comprehensively summarizes the current research progresses in polymyxin sensitizers particular focusing on three aspects: natural compounds, synthetic small molecules, and drug repurposing. Furthermore, this paper explores the innovative strategies of gene intervention, new targets, and nanotechnology-based formulations in the development of sensitizer, aiming to provide systematic theoretical support and research ideas against polymyxin resistance.