Available information associated with Calotropis procera posted its phytotoxic effect as bio-herbicide scarce works studied its stimulatory/nutritive effect. A pot experiment was performed to assess the validity of using Calotropis procera (C. procera) leaves extract as a bio-stimulant for the growth and quality of a medicinal plant Catharanthus roseus (C. roseus) evaluated by some physio-biochemical indices. Different types of C. procera leaves extracts (CLEs) (methanolic, cold water and autoclaved water extracts) were delivered by two different modes of application. The results revealed that application of CLEs as irrigation or foliar spraying caused a stimulation effect on C. roseus plant. Root and shoot length, dry and fresh weight were significantly improved due to CLEs applications. C. roseus bioactive molecules such as anthocyanins, phenolics, flavonoids, alkaloids, ascorbic acid, reduced glutathione and α-tocopherol were abundance increased significantly with CLEs applications. Reactive oxygen species (ROS) decreased explaining the involvement of CLEs in induction of antioxidant enzymes catalase, ascorbate peroxidase, polyphenol oxidase, guaiacol peroxidase and glutathione-S-transferase for modifying cell oxidative status witnessed by lower lipid peroxidation that kept below the untreated plants’ baseline reflected the improvement of growth and quality rather than phytotoxic effect. The promotion of wholesome-promoting secondary metabolites by CLEs was closely correlated to elevated phenylalanineammonialyase activity. The comparable efficient effect induced by all treatments might be judged by the relation between C. procera …