A series of pyridinium aldoximes having a sugar conjugated to the pyridine ring has been prepared as potential antidotes against organophosphate poisoning. The sugar residue was attached either directly through C-1 or C-6 of the pyranose ring or through a C3 bridge between the glycosyl group and the nitrogen atom of the pyridine moiety. Attachment of a sugar group to the oxime derivative seems to increase the bioavailability of the antidote. The clearance rate of the sugar conjugates was significantly lower than that of their non-sugar analogs and thus they were retained longer in the blood circulation. The sugar derivatives were more potent in decreasing paraoxon-induced hypothermia (which is regulated within the central nervous system) than N-methyl-2-pyridiniumaldoxime methanesulfonate, one of the most commonly used mono-oximes. The sugar analogs were also less toxic than the non-sugar analogs; some also displayed higher efficacy. The mechanism underlying the improved features of the sugar oximes, and the structural requirements in relation to the sugar attachment to the oxime function, are discussed.