Kalmegh [Andrographis paniculata (Burm. F.) Wall ex. Nees] has industrial potential due to the presence of bioactive substances, which always upsurges its demands in the pharmaceutical industry. The purpose of the present study was to identify the suitable companion crops (cereal crops: maize, pearl millet, and sorghum; vegetable crops: okra, cluster bean, tomato, and brinjal; oilseed crops: sunflower and sesame; and pulses crop: pigeon pea) in kalmegh based intercropping system. To accomplish this goal, a field experiment was conducted at the experimental research farm of the Council of Scientific and Industrial Research - Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP) Lucknow, India, for three successive years. The results of the experiment revealed that among all the treatments of intercrops, T10 (Kalmegh + Pigeon pea), T4 (Kalmegh + Okra) in vegetables, T2 (Kalmegh + Pearl millet) in cereals had significantly higher kalmegh dry herbage yield (increased by 30.55%, 29.32%, and 16.53%, respectively), and andrographolide yield (increased by 87%, 49.09%, and 53.17%, respectively) in comparison to kalmegh sole-crop, this is likely related to the sciophytic behavior of kalmegh. Although, kalmegh shows strong competitiveness with all the treatments except T6 (Kalmegh + Tomato), T7 (Kalmegh + Brinjal), and T9 (Kalmegh + Sesame). In a similar manner, the land equivalent ratio ranged from 1.37 to 2.19 and the area time equivalent ratio ranged from 1.25 to 2.0, demonstrating that the kalmegh based intercropping system is a beneficial approach to maximize resource use efficiency. Consequently, in a world facing limited land resources, our research outcomes could help smallholder’s in improving their agricultural systems to achieve greater production efficiency.