Pestalotiopsis species were most dominant endophytic species isolated from four medicinal plants including Terminalia arjuna , Terminalia chebula , Azadirachta indica , and Holarrhena antidysenterica . Thirty Pestalotiopsis species isolated from different parts of the medicinal plants were selected for the study. The antioxidant and antihypertensive properties of Pestalotiopsis isolates were determined by measuring 1,1-diphenyl-2-picrylhydrazyl inhibitory activity, lipid peroxidation, and angiotensin-converting enzyme inhibition activity. Pestalotiopsis isolates of T. arjuna origin exhibited maximum radical scavenging activity compared with the others. The IC50values of Pestalotiopsis extracts for 1,1-diphenyl-2-picrylhydrazyl scavenging activity ranged from 14 to 27 μg/mL compared with 15 and 6 μg/mL for butylated hydroxytoluene and ascorbic acid, respectively. The DNA damage study was also done for three isolates, TC-315, TA-37, and TA-60; TA-37 gave 80% protection. The IC50values of Pestalotiopsis extracts for lipid peroxidation ranged between 30 and 35.5 μg/mL, while for the positive control butylated hydroxytoluene, it was 26 μg/mL. Out of 32 fungal extracts screened for antihypertensive assay, five (TA-37, TA-60, TA-102, TA-103, and TC-320) showed >60% inhibition of angiotensin-converting enzyme. The IC50values for five extracts ranged from 21 to 37 μg/mL and was 20 μg/mL for captopril used as a positive control. The antibacterial activity was measured by the microplate-based turbidity measurement method. Four Pestalotiopsis extracts (TA-04, TA-37, TA-60, and TA-102) showed >75% inhibition against five bacterial strains including Bacillus subtilis , Escherichia coli , Pseudomonas fluorescens , Xanthomonas axonopodis pv. malvacearum, and Staphylococcus aureus . The antioxidant, antibacterial, and antihypertensive activities demonstrated the potential of Pestalotiopsis extracts as therapeutic targets.