A colon-targeted drug delivery system is preferred as a means of drug delivery towards the colon to treat several colon-specific diseases, particularly colon cancer and inflammatory bowel disease. Utilizing colon-targeted drug delivery systems may result in minimized premature drug release or degradation while at the same time increasing local colonic drug delivery. On the other hand, lipid nano-carrier is another alternative drug delivery system that can increase drug solubility, enhance drug permeation and retention, and offer its surface for further specific modification. Several lipid nano-carriers, such as nanoemulsion, liposome, lipid-polymer hybrid nanoparticle, solid lipid nanoparticle, and nanostructured lipid carrier, have already been or are potentially being used as colon-targeted drug delivery systems. Various applications of lipid nano-carriers in colon-targeted drug delivery system mechanisms have also been identified, both in their original and modified forms, namely pH-dependent, microflora-dependent, time-dependent, surface modification, and combination approaches. The combination of lipid nano-carriers and various colon-targeted drug delivery mechanisms offers several advantages, proven with in vitro and in vivo results. Several highlighted findings, such as increased drug solubility, permeability, and cellular uptake; controlled release profile, improved colon-targeted delivery, reduced side effects and toxicity; increased pharmacokinetics parameters (AUC, Cmax, Tmax, mean residence time); and positive pharacodynamic results have been reported. Based on these findings, modification of lipid nano-carriers for colon-targeted drug delivery system purposes offers a potential prospect in treating colon-specific diseases. © 2025 Elsevier B.V.