Among non-essential heavy metals, cadmium (Cd) pollution in soil continuously increasing by anthropogenic activity such as agriculture fertilizer and industrial sources worldwide and have several harmful impacts on plants and humans. Andrographis paniculata is a highly medicinal plant having diverse range of SMs like andrographolide (AG). The present study was carried out to investigate the effect of Cd on growth, activity of antioxidative enzymes and andrographolide production of A. paniculata. Cd was applied as cadmium chloride (CdCl2) at 5, 10 and 15 μg g−1 of soil. All the studied treatments of Cd were found to be toxic for A. paniculata. The root-shoot length, root-shoot fresh weight, root-shoot dry weight decreased with increasing concentrations of Cd. Total phenolics and flavonoids content significantly increased with increasing Cd concentration in soil. The activity of catalase (CAT), peroxidase (POX), ascorbate peroxidase (APX), glutathione reductase (GR), guaiacol peroxidase (GPX) and polyphenol oxidase (PPO) increased with increasing concentration of Cd compared to control plants. The maximum activity of CAT, POX, APX, GR, GPX and PPO was observed at 15 µg Cd g−1. The AG content in the leaves of plants increased with Cd application. Maximum AG content was observed at 10 μg g−1 applied dose of Cd. Out of the concentrations studied 5 and 10 μg g−1 were moderately toxic to A. paniculata and produced maximum amount of AG.