During the past few decades, interest in phenolic substances found in aquatic environments has increased because of their extensive uses in many industries, which have a high degree of toxicity. This study aimed to investigate removing phenol from contaminated wastewater using environmentally friendly synthesized nanoscale-activated carbon derived from reed stalks as an adsorbent. This study aimed to examine removing phenol from contaminated wastewater using environmentally friendly synthesized nanoscale-activated carbon derived from reed stalks as an adsorbent. The prepared adsorbents were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray (EDAX) and Fourier transform-infrared (FTIR) spectroscopy. Four distinct factors were studied using the statistical design of experiments, data analysis (Design Expert Software), and a central fitting design (CCD) using a response surface methodology (RSM) to maximize the phenol elimination. The four variables were the initial phenol concentration (30–120 ppm), pH (2–11), the concentration of adsorbent (50–600 ppm), and reaction time (30–120 minutes) introduced as input data to the model predicted the removal efficiency (%) of phenol. The ANOVA analysis was conducted to examine the accuracy and significance of the model. The ANOVA test suggests that the second-order quadratic model is the most effective in explaining the process of phenol elimination, and the predicted data have strong agreement with the corresponding experimental values. The results revealed that are as follows: initial phenol concentration of 30 mg/L, pH of 2, adsorbent dose of 600 mg/L, contact time of 120 minutes, and adsorption capacity of 30.0825 mg/g were the optimal adsorption conditions obtained from the experimental work. These findings indicate that the nano-activated carbon produced from reed stalks is an effective adsorbent for removing phenol from wastewater.