Climate change is causing many environmental problems that impact human health. Extreme environmental conditions affect the immune of the human body. It is easily exposed to the disease. The community takes various precautions to improve the immune system. One of them is to use medicinal plants as an endurance enhancer because some medicinal plants contain immunomodulators. Biduri (Calotropis Gigantea) is one of the medicinal plants that allegedly serves as an immune stimulator or immunosuppressive antibody production. Biduri has not been cultivated by the community, growing wildly. Research using Azolla and mycorrhizal was conducted as an effort to domesticize Biduri and prepare the source of medicinal raw material. The research aims to study the effect of Azolla and mycorrhiza on the vegetative growth of biduri. The study used 5 levels of Azolla, namely 0, 5, 7.5, 10, and 12.5 tons ha−1, and 4 levels mycorrhizal, namely 0, 5, 10, and 15 tons ha−1. Treatment combinations are arranged based on a Randomized Complete Block Design and repeated 6 times. The vegetative growth including the plant height, number of leaves, number of leaves, leaf width, leaf length was measured at 12 weeks after transplanting. The response of vegetative growth on Azolla and mycorrhizal application showed the same pattern, the application of mycorrhizal has not shown a difference in height or development of biduri leaves, while the application of Azolla 12.5 tons ha−1 increases the height of plants and leaves development significantly compared to without Azolla.