<p>Water bodies that are adversely affected due to heavy metal pollution are rendered unsafe both for drinking and irrigation purposes. Hydrophytes such as <i>Pistia stratiotes</i> L.&#xa0;(water lettuce) have tremendous remediation potential for heavy metals (HMs). However, studies on ecophysiological responses along with heavy metal tolerance to dose-dependent cadmium (Cd) and lead (Pb) are scant. This research evaluated the bioremediation potential and ecophysiological responses of <i>P. stratiotes</i> L.&#xa0;(water lettuce) by treating plants to varying CdCl₂ and PbCl₂ concentrations. Growth, morpho-anatomical and mitigation to stress responses in <i>P. stratiotes</i> L.&#xa0;were studied to understand phytoremediation strategy. The physico-chemical water analyses showed that heavy metal concentration directly affected pH, total dissolved solids, and electrical conductivity. The uptake of Cd and Pb in <i>P. stratiotes</i> L.&#xa0;roots was much higher (62 and 82% respectively) than in leaves at 15&#xa0;mg L⁻¹. Plants treated with (5&#xa0;mg L⁻¹) Pb and Cd maintained growth and physiological parameters due to enhanced activity of peroxidase and catalase enzymes and higher total phenols as well as leaf proline. Metal phytotoxicity was more pronounced at 15&#xa0;mg L⁻¹ than at low and moderate concentrations of Cd and Pb in <i>P. stratiotes</i> L.&#xa0;Plants exposed to 5 and 15&#xa0;mg L⁻¹ Pb showed reductions in chlorophyll compared to control plants. Similarly, the concentration of chlorophyll b was reduced by 64% and carotenoid content by 43% in plants treated with 15&#xa0;mg L⁻¹ Pb compared to the control plants. Plants showed&#xa0;decreased aerenchyma, parenchyma, vascular tissues, and trichome length under increasing Cd and Pb concentrations. The sustainable strategies of water lettuce to adapt and mitigate metal contamination could serve in ecological restoration and decontamination of water bodies for environmental safety.</p>