Giant reed () has proved to be effective in detoxification, accumulation and tolerance of toxic metals. The present study explored the stress response of giant reed against Cu and Ni stress. The effect of metal stress was studied on dry weight, chlorophyll pigments antioxidant enzymes production and selected genes expression. The accumulation of heavy metals increased in a concentration-dependent manner and depicted toxicity symptoms in leaves beyond 75 mg/L of Cu or Ni. Oxidative stress was evident in giant reed under highest exposure of Ni and Cu which increased antioxidants activities (SOD, POD and CAT). It was observed that metal transport and detoxification were possible due to the expression of glutathione reductase, Natural Resistance-Associated Macrophage Protein (NRAMP) and Yellow Stripe-Like (YSL) genes. These insights into the genetic basis of a successful remediating plant species will be useful in understanding heavy metals tolerance in giant reed.