In this work, we present the synthesis and the anti-trypanosomal activity of the 2-(4-(adamant-1-yl)phenyl)-N-hydroxyarylamides, 1a,b and the 2-(4-(adamant-1-yl)phenoxy)-N-hydroxyacetamide, 1c. The 4-(adamant-1-yl)phenyl- and 4-(adamant-1-yl)phenoxy- moieties, which are endowed with promising drug-like properties, are functionalized at the side chain termini as hydroxamic acids. The phenoxy acetohydroxamic derivative, 1c, shows the most interesting profile in terms of activity and toxicity against trypanosomes and merits further investigation.