The present study investigates the effect of soil amended with sewage sludge on oxidative changes in zucchini and cucumber plants (Cucurbitaceae) and the consequent activation of their antioxidative systems and detoxification mechanisms. The plants were grown in pots containing soil amended with three concentrations of sewage sludge (1.8 g, 5.4 g and 10.8 g per pot), while controls were potted with vegetable soil. The activities of three antioxidative enzymes, ascorbate peroxidase (APx), catalase (CAT) and guaiacol peroxidase (POx), were assessed, as well as of the detoxifying enzyme S-glutathione transferase (GST). Lipid peroxidation was evaluated by measuring the extent of oxidative damage; α-tocopherol content, the main lipophilic antioxidant, was also measured. Visible symptoms of leaf blade damage after sewage sludge application occurred only on the zucchini plants. The zucchini and cucumber plants showed a range of enzymatic antioxidant responses to sewage sludge application. While APx and POx activities increased significantly with increasing sludge concentration in the zucchini plants, they decreased in the cucumber plants. Moreover, although the activity of these enzymes increased gradually with increasing doses of sewage sludge, these levels fell at the highest dose. An inverse relationship between peroxidases activity and CAT activity was observed in both investigated plant species. In contrast, although GST activity increased progressively with sludge concentration in both the zucchini and cucumber leaves, the increase in GST activity was greater in the zucchini plants, being visible at the lowest dose used. The results indicate that signs of sewage sludge toxicity were greater in zucchini than cucumber, and its defense reactions were mainly associated with increases in APx, POx and GST activity.