This study has been designed to develop palm oil (PO) based organogels using span 80/tween 80 mixture (OG) as a gelator system by fluid-filled structure mechanism. The results suggested formation of organogels, emulsions, and microemulsions as the proportions of PO, OG and water were varied. The emulsions were found to be thermodynamically unstable as compared to the organogels and the microemulsions. Accelerated thermal stability test suggested that all the microemulsions and the organogels of only eight compositions were stable. The organogels showed viscoelastic property while the microemulsions showed viscous flow behavior. Both the organogels and the microemulsions were found to be highly hemocompatible and nonirritant. The antimicrobial efficiency of the ciprofloxacin HCl-loaded formulations showed equivalent efficiency as compared to marketed formulations. The rates of drug release from the organogels were found to be relatively slower as compared to the microemulsions. The preliminary studies suggested that the developed organogel and microemulsion-based formulations may be tried for topical delivery of antimicrobials. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014, 131, 39979.