Inorganic Te(IV) compounds are important cysteine protease inhibitors and antimicrobial agents; AS-101 [ammonium trichloro (dioxoethylene-O,O′)tellurate] is the first compound of a family with formula NH4[C2H4Cl3O2Te], where a Te(IV) centre is bound to a chelate ethylene glycol, and showed several protective therapeutic applications. This compound is lacking in stability performance and is subjected to hydrolysis reaction with displacement of the diol ligand. In this paper, we report the stability trend of a series of analogues complexes of AS-101 with generic formula NH4[(RC2H3O2)Cl3Te], where R is an alkyl group with different chain length and different electronic properties, in order to find a correlation between structure and stability in aqueous-physiological conditions. The stability was studied in solution via multinuclear NMR spectroscopy (1 H, 13C, 125Te) and computationally at the Density Functional Theory level with an explicit micro solvation model. The combined experimental and theoretical work highlights the essential role of the solvating environment and provides mechanistic insights into the complex decomposition reaction. Antimicrobial activity of the compounds was assessed against different bacterial strains.