Compounds containing biguanide moiety, such as buformin, phenformin, and metformin are well recognized for their antihyperglycaemic action. Imeglimin is a dihydro-1,3,5-triazine that can be considered as a cyclic metformin derivative, which has been tested as a promising new antidiabetic drug. Quantum-chemical calculations have been carried out to examine its structure and its gas-phase basicity toward the proton and the lithium cation. Owing to various structural isomeric rearrangements possible for imeglimin, 23 isomers have been considered for the neutral molecule in vacuo at the B3LYP/6-311+G(d,p) level. Four isomers (two major and two minor) have been selected and their exceptional energetic stabilities additionally confirmed by the G2, G2MP2, and G4 methods. The major isomers (>95%) correspond to the push–pull biguanide systems, which are similar to those for neutral metformin. The minor isomers (<5%) have nonanalogous metformin structures. The basicity properties in the gas phase have been examined by computing the energetics of protonation and adduct formation with Li⁺. The same protocol (starting by density functional theory, then Gn procedures) used for the neutral molecule was applied to the monoprotonated and monolithiated forms of imeglimin to select the favored isomers. When compared to metformin, the proton affinity of imeglimin is larger by more than 10 kJ mol^–1, this increase being attributed to the effect of the additional >CH–CH₃ group. The cyclic form of imeglimin precludes the possibility of chelation effect by two imino groups as it occurs for metformin. Consequently, imeglimin has a lower lithium-cation affinity than that of metformin by ca. 30 kJ mol^–1. The lithium cation seems however to be weakly chelated by the neighboring imino and amino N atoms of imeglimin, an effect that is weaker than that of the two terminal imino N atoms of metformin. Gas-phase proton basicity of imeglimin falls between that of bicyclic amidine DBU and guanidine TBD, whereas lithium-cation basicity is situated between that of bicyclic guanidine MTBD and tricyclic vinamidine TTT. Electron delocalization in the biguanide moiety of imeglimin is analogously related to isomerism as that in the parent biguanide and metformin.