The aim of this study was to analyse the species composition, structures, and regeneration of woody plant species and the impacts of site factors on the natural regeneration of tree species in four study sites of MFBR. The vegetation data were collected systematically in 140 plots with the size of 400 m2 for trees; 25 m2 for seedlings, saplings, shrubs, and lianas; and 1 m2 for herbs. Individual tree and shrub DBH ≥ 5 cm were measured and counted. The diameter at breast height (DBH), frequency, basal area, importance value index (IVI), and density were used for vegetation structure description and regeneration. A total of 158 plant species belonging to 115 genera, 56 families, and 80 species (51%) trees, 26 (16%) shrubs, 19 (12%) herbs, and 33 (21%) lianas were identified and recorded. The most dominant families were Euphorbiaceae, Rubiaceae, and Moraceae, each represented by 13 species (7.4%), 12 species (6.8%), and 10 species (5.7%), respectively. The tree densities varied from 1232 to 1478 stem ha−1, sapling density 176.8 to 708.7 stem ha−1, and seedling density 534.7 to 1657.5 stem ha−1, with an average basal area of 63.6 m2 in the study sites. Dracaena afromontana was the most frequent woody species in the MFBR occurring in 90% followed by Celtis zenkeri (65%) and Pouteria altissima (62.5%). The regeneration status of all the woody plant species was categorised as “not regenerate” (9.6%), “poor” (30.7%), “fair” (59.5%), and “good” (10.8%) in all sites. The correlation result between natural regeneration and site factors revealed both positive and negative relationships. However, the main threat to the biosphere reserve is illegal logging for different purposes. Therefore, awareness creation on sustainable forest management, utilisation, conservation of priority species, and livelihood diversification to the local community and encouraging community and private woodlot plantation in the transitional zone of biosphere reserves are recommended.