The effect of long-alkyl-chain amines in CuI-assisted azide–alkyne cycloadditions of terminal alkynes with organic azides in glycerol and other environmentally benign solvents (water, ethanol) has been examined. The presence of these additives favors the in situ formation of Cu^I-based nanoparticles and results in an increase of the catalytic reactivity. In glycerol, liquid-phase transmission electron microscopy (TEM) analyses, enabled by the negligible vapor pressure of this solvent, proved that Cu^I nanoparticles are responsible for the observed catalytic activity. The wide variety of alkynes and azides of which this effect has been investigated (14 combinations) confirms the role played by these additives in Cu-catalyzed Huisgen cycloadditions.