In this study, two new deep eutectic mixtures were prepared via combination of D-fructose with urea and L-aspartic acid or L-arginine. After identification, the catalytic activity of these mixtures, was evaluated in the one-pot multi-component synthesis of tetrahydro-1,2,4-triazolo[5,1-b]quinazolin-8(4H)-one derivatives. In the presence of both prepared mixtures the desired products were obtained with high diversity from the reaction of 3-amino-1,2,4-triazole, aromatic aldehydes and dimedone or cyclohexanedione in short reaction times with good yields. The reported methods have notable features such as easy preparation of the catalysts, green processes, cost-effectiveness and simple work-up procedures. Addintionally, the catalysts are easily recoverable and can be recycled up to five times without substantial loss of their activity.