N-acylethanolamides are naturally occurring hydrophobic molecules usually present in a very small amount in many mammalian tissues and cells. The presence of N-acylethanolamides has also been demonstrated in human reproductive tracts and fluids, although their biological effects and molecular mechanisms of action are not yet completely elucidated. It is known that some N-acylethanolamides, such as oleoylethanolamide, have antioxidative properties. The aim of this study was to test whether oleoylethanolamide could protect sperm cells from reactive oxygen species-induced oxidative damage in cases of idiopathic infertility, because the excessive generation of these radicals was associated with this pathology. Our results show that 2.5 nM oleoylethanolamide in vitro supplementation significantly reduces DNA strand breaks both in fertile and infertile subjects. Moreover, oleoylethanolamide increases kinematic parameters, such as curvilinear velocity and amplitude of lateral head displacement and hyperactivation, both in the presence and in the absence of oxidative stress. Results of this study support the hypothesis of a possible protective action of oleoylethanolamide against reactive oxygen species, which could explain its beneficial effects on in vitro capacitated spermatozoa.