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HIV/AIDS pandemic is currently the most socio-economic challenge that faces Tanzania as it affects mostly the young and most economically productive population. People living with HIV/AIDS in Tanzania are susceptible to fungal and bacterial opportunistic infections, which are a major cause of mortality and morbidity in the country. Despite the government’s intervention to provide ARVs to people living with HIV/AIDS, many of them especially those living in the rural areas can neither afford them due to poverty nor access them due to distance to health centers. Moreover, resistance of opportunistic microbial pathogens to conventional medicines and the serious side effects associated with antiretroviral drugs are also a major drawback to the management of HIV/AIDS in the country. Due to these factors, many people opt to use of traditional medicines. This paper highlights the use and conservation of herbal remedies to manage HIV/AIDS pandemic in Tanzania. Ethnobotanical surveys were carried out in Bukoba Rural District to explore the traditional ethno-medical knowledge, the use and conservation of medicinal plants in the management of HIV/AIDS opportunistic infections and to determine whether levels of harvesting are sustainable. The district is currently an epicenter of HIV/AIDS and although over 90% of the population in the district relies on traditional medicines to manage the disease, this traditional knowledge still remains largely unknown. Seventy-five plant species belonging to 66 genera and 40 families were found to be used to treat one or more HIV/AIDS related diseases in the district. Eight plant species were tested in-vitro for their antifungal activity against three major fungal pathogens, Candida albicans (C.P. Robin) Berkhout, Cryptococcus neoformans (San Felice) Vuill., and Aspergillus niger Tiegh. Three of them were further tested in-vivo for their anti-Candida activity. With decreasing natural stocks of medicinal plants, and based on the results, this study further provides concrete recommendations for the conservation of these important non-timber forest products and the region’s medicinal plant biodiversity.