Calotropis procera (Ushar) leaves are frequently used in traditional medicine to treat several diseases. However, the plant contains toxic compounds rendering it unsafe material. Hence, the objective of this study was to treat C. procera dried leaves powder by bioprospecting for fungal endophytes to be a safe applications. Three selected fungal isolates including Cladosporium sphaerospermum, Cochliobolus lunata and Cochliobolus sp.were used for the reduction of C. procera dried leaves powder toxicity. Sporulation of each of these fungi was increased in the presence of 2 g more than 1 g of dried leaves powder in PDB media at 25°C within 4 weeks of incubation. Also, C. sphaerospermum, Cochliobolus sp., and C. lunata were tested for their ability to reduce the toxicity of C. procera dried leaves powder by using thin-layer chromatography (TLC). Only C. sphaerospermum showed the ability to reduce the Calactin toxin presented in powdered leaves Furthermore, the toxicity test of dried leaves powder treated by C. sphaerospermum showed significant (100%) survival of the adult earthworm Lumbricusrubellus compared to the negative control, which induced 100% mortality of worms. These results were also comparable with C. sphaerospermum powdered mycelium, which showed no signs of toxicity. It can be concluded that fungal endophytes such as C. sphaerospermum are promising candidates for eliminating leaves toxicity.