Heavy metal (HM) pollution of marine coastal areas is a big concern worldwide. The marine phanerogam Posidonia oceanica (L.) Delile is widely considered to be a sensitive bioindicator of water pollution due to its ability to sequester trace elements from the environment. The analysis of specific biomarkers, like reactive oxygen species scavengers, could allow us to correlate the physiological response of P. oceanica meadows to water pollution. In this study, we analysed the activity of some antioxidant enzymes and the expression level of the corresponding genes in the leaves of P. oceanica plants harvested from four meadows distributed along the Tyrrhenian coast; lipid peroxidation and the expression level of two genes related to HM response, metallothionein-2b and chromethylase, were also measured. The results of biochemical and molecular analyses were correlated with the concentration of some HMs, such as Cr, Cd, Cu, Ni and Pb, measured in P. oceanica leaves. We found a very strong antioxidant response in plants from the Murelle meadow whose HM concentration was the lowest for most of the analysed HMs, particularly Cu.