Abstract Gebel Elba is one of the three coastal mountains in the southeast corner of Egypt facing the Red Sea and it is rich in medicinal plants. Twenty fungal species belong to 14 genera were isolated as endophytic fungi from the medical plants Salvia aegyptiaca L. and Balanties aegyptiaca L. collected from Gebel Elba. The highest colonization frequency 21.38, 20.64, 20.00, and 14.71% along with relative percentage occurrence 17.28, 16.69, 16.17 and 11.89 were recorded to Alternaria alternate, Humicola grisea, Colletotrichum sp. and Trichoderma viride in Salvia aegyptiaca but the predominant fungal species in the microbiota of Balanties aegyptiaca were Curvularia papendorfii, Cylindrocephalum sp., Chaetomium globosum, Nigrospora sphaerica and Trichoderma harzianum with colonization frequency of 23.03, 17.30, 15.00, 13.08 and 12.22% with relative percentage occurrence values 17.60, 13.22, 11.47, 9.99 and 9.34, respectively. Phytochemical analysis revealed the presence of flavonoid, saponin, tannin, sterol, quinone, terpenoid, coumarin and anthraquinone metabolites in 80.77, 50.00, 88.46, 65.39, 42.31, 76.92, 84.62 and 61.54%, respectively. The highest content of phenolic (97.23 ± 1.0 mg/g) was detected in the ethyl acetate extract of endophytic Aspergillus terreus isolated from Balanties aegyptiaca but the maximum yield of flavonoid (79.86 ± 0.04 mg/g) and tannin (35.07 ± 0.05 mg/g) were detected in endophytic Alternaria alternate and Humicola grisea isolated from Salvia aegyptiaca. Furthermore, Salvia aegyptiaca and Balanties aegyptiaca associated endophytic fungal microbiota showed potent antibacterial, antioxidant and anticancer activities. This work revealed that fungal endophytes inhabited these Egyptian medicinal plants could be effective source for bioactive compounds useful for developing better antioxidant, antibacterial or anticancer drugs with good therapeutic index value.