The contamination of water by heavy metals is a worldwide environmental problem. Phytoremediation and constructed wetlands have become increasingly popular as more sustainable and environmentally friendly techniques of removing heavy metals from the wastewater. This study, therefore, investigated the phytoremediation of nickel by Alocasia puber (A. puber) in a constructed wetlands (CW) microcosm. This study identified the optimum conditions for nickel (Ni) removal from wastewater using response surface methodology (RSM) with central composite design (CCD). Two operational variables were assessed: exposure time and initial Ni concentration. The optimum conditions for the maximum removal of Ni from water were an exposure time of 10 days and 99.76 mg/L initial Ni concentration. The results indicated that 95.6% removal was achieved under the optimized conditions, with a high correlation coefficient (R² = 0.97) between the statistical model and the experimental data. Field emission scanning electron microscopy images showed anatomical changes in the A. puber samples due to Ni exposure, and transmission electron microscopy images revealed some internal damages in the A. puber, but visual Ni toxicity symptoms, such as necrosis and chlorosis, were not observed in the A. puber. This study demonstrated that A. puber planted in a constructed wetland microcosm was able to remediate wastewater contaminated with Ni.