The present work deals with preparation of the olive oil (OO) based organogels using sorbitan monostearate (SMS) and sorbitan monopalmitate (SMP) as organogelators for controlled drug delivery applications. Metronidazole (MZ) was used as the model drug. Gels were prepared by solubilizing the organogelators in OO at 60°C under stirring. As the solution was cooled down, the gelator molecules precipitate as an isotropic phase having networked structures, which immobilized OO. Formation of 3D networked structure was confirmed by light, phase contrast, and scanning electron microscopy. Accelerated thermal stability studies demonstrated the thermal stability and thermoreversibility of the organogels. DSC and gel disintegration studies suggested that the SMS based organogels were having higher thermal and physical strength as compared to the SMP based organogels. Viscometric analysis suggested the pseudoplastic flow behavior of the gels. The SMS organogels were more amorphous as compared to the SMP organogels of same composition. Drug release from the organogels followed Fickian diffusion kinetics. The drug loaded gels have shown good antimicrobial property against Escherichia coli and Bacillus subtilis and were found to be highly hemocompatible in nature. On the basis of the preliminary results, the developed organogels can be used as matrices for the topical drug delivery. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013