Deforestation in Ugandan Tropical Rainforest Reserves as threat to natural medicine is still undocumented. In this study, we reviewed literature on deforestation most especially from 1990-2020 in the Tropical Rainforest Reserves. We examine the trend of deforestation, impact of deforestation on medicinal plant species’ and threatened medicinal plant species in the Tropical Rainforest Reserves in Uganda. Secondary data from National Forestry Authority on deforestation (1990-2020) was analysed to determine the trend of forest deforestation while PubMed®, Google Scholar, and SCOPUS databases were also used to provide information on the threatened medicinal plants. Our results show that there has been an annual incredible decline of 17% in the trend of deforestation both in Tropical Rainforest Reserves (low-stocked and well-stocked). The results of the review also noticed a 0.86 strong positive correlation in the decline of both Tropical Rainforest Reserves. This review also documented 13 medicinal plants as the most threatened in the Ugandan Tropical Rainforest Reserves. The medicinal plants in Uganda include Dioscorea bulbifera, Cytropsis articulata, Prunus africana, Warburgia ugandensis, Entandrophragma utile, Irvingia gabonensis, Spathodea campanulate, Aloe ferox, Vernonia amygdalina, Erythrina abyssinica, Moringa oleifera, Hoslundia opposita Vahl and Milicia excelsa. Our study articulates human activities that are affecting medicinal plants include agricultural expansion, timber harvesting, charcoal burning, firewood harvesting, weak forest policies and laws, un clear forest boundaries infrastructure development e.g., roads.