<p>The rapid spread of multidrug-resistant bacteria, especially those resistant to the last-line treatment, colistin, has created an urgent demand for alternative or adjunctive therapies. In this context, natural compounds have attracted attention for their intrinsic antibacterial properties and potential to synergize with existing antibiotics. Recent studies have highlighted several natural compounds, including quercetin, cinnamaldehyde, thymol, eugenol, carvacrol, resveratrol, curcumin, farnesol, and apigenin, with notable inhibitory effects against colistin-resistant bacteria. Beyond their independent antibacterial activity, these compounds have shown synergistic interactions with colistin. Their combination reduced the minimum inhibitory concentration (MIC) of colistin and, in some cases, even restored bacterial susceptibility to it. These compounds exert their effects through mechanisms such as interacting with the MCR-1 protein to inhibit its function, downregulating virulence gene expression, and suppressing efflux pumps. Natural compounds can inhibit biofilm formation and disrupt mature biofilms. By compromising membrane integrity, they promote leakage of intracellular contents and also enhance antibiotic penetration. Promising results from in vivo studies using animal models indicate the potential of these compounds for clinical application. Nonetheless, further research is essential to fully validate their safety and effectiveness before clinical implementation. This review aims to provide a comprehensive overview of the antibacterial properties and mechanisms of action of natural compounds against colistin-resistant bacteria, with a special focus on their potential to restore colistin efficacy. It aims to guide future research and support the development of clinically applicable treatment strategies.</p>