Plants that belong to the Combretaceae family have long history of use in the traditional medicine systems of Africa and Asia for treatment of diseases and conditions associated with HIV/AIDS-opportunistic infections. The objective of this study was to investigate the biological activities of extracts of Terminalia stenostachya Engl. & Diels and Terminalia spinosa Engl. (Combretaceae), to verify the rationale for their use by traditional health practitioners in the treatment of HIV/AIDS patients in Tanzania. Extracts of the leaves, stem barks and roots of T. stenostachya and extracts of stem barks and roots of T. spinosa have all shown strong activity against a number of standard microbial strains including Mycobacterium madagascariense and Mycobacterium indicus pranii, Streptococcus faecalis, Staphylococcus aureus, Vibrio cholera, Bacillus anthracis, Bacillus subtilis, Klebsiella pneumoniae, Salmonella typhi, Pseuodomonas aeruginosa and Escherichia coli. All extracts from the two plant species showed strong antimycobacterial activity against test organisms. The stem and root bark extracts were more active than leaves against both gram positive and negative bacteria. With the exception of two extracts from stem barks of T. spinosa, all other extracts from T. stenostachya and T. spinosa that were tested exhibited less activity against brine shrimp larvae with LC50 values ≥ 100 μg/mL compared to cyclophosphamide, a standard anticancer drug. These results provide an indication that these plants may possess therapeutically potent antimicrobial compounds worth further development.