The intensification of modern agriculture may impact amphibian populations through habitat loss and the direct and indirect effects of the pesticides upon which it relies. The increased homogeneity of modern agricultural landscapes may be detrimental in times of extreme low and high temperatures associated with climate change, as refuge abundance and habitat connectivity decrease. In this study, we evaluated the impacts of the herbicide glyphosate and subsequent intense drought on the Common Tree Frog, Hypsiboas pulchellus, inhabiting an agricultural landscape. We examined a series of organismic indices (stomach content index, hepatosomatic index, body fat index, gonadosomatic index, condition factor) as well as biomarkers of oxidative stress (hepatic catalase activity and reduced glutathione [GSH] content), exposure to contaminants (hepatic gluthatione-S-transferase activity), and genotoxicity (frequency of micronuclei). No significant differences were observed in the parameters measured when comparing frogs sampled before, 2, and 15 days after glyphosate exposure. However, anurans sampled in the same site two months later, when a drought was at its peak, presented a decrease in stomach content and hepatosomatic index, as well as an increase in hepatic catalase activity, hepatic GSH content and micronuclei frequency in peripheral circulating erythrocytes. Our findings demonstrate that drought is challenging to these anurans in this environment as evidenced by an apparent reduction in food intake and oxidative stress.