To study endophytic fungi associated with two plant species used as ethno-medicines by aboriginal tribes of Similipal Biosphere Reserve and evaluation for their antimicrobial potentials against some clinically significant human pathogens. A total of 458 endophytic isolates were obtained from leaf, stem and fruit tissues of Solanum rubrum and Morinda pubescence. The dominant endophytic fungi belong to genera Aspergillus, Colletotrichum, Curvularia and Mycelia sterilia. Maximum endophytic isolates were obtained from leaves segments followed by stem and fruit tissues. In both the plants class hypomycetes were dominant over other fungal classes. Shannon-Weiner and Simpson indexes showed rich diversity of endophytic fungi suggesting even and uniform occurrence of various species. The endophytic isolates showed varying degree of antimicrobial activity against 9 human pathogens. In S. rubrum 20% and 10% of the isolates inhibited all the Gram-positive and Gram-negative bacteria and 35% of the isolates displayed antifungal activity against all the test fungal pathogens. One of the isolate showed considerable antimicrobial activity against all the test pathogens. Endophytic isolates of M. pubescence showed 24% antibacterial activity against Gram-positive bacteria and 28% antifungal activity against all the test fungal pathogens. The study revealed that medicinal plants associated endophytes could be a rich source of antimicrobial agents.