Medicinal plants are known to contain phytometabolites that could effectively improve an individual’s state of health. Species of Combretum are highly valued in Africa due to the plethora of their traditional medicinal uses. Combretum erythrophyllum. Burch. Sond., commonly known as the river bushwillow, is known to contain medicinally important phytometabolites. Traditionally, the foliage is used to treat venereal diseases and abdominal pain, whilst the bark is used to alleviate sores, infertility, and labour pains. Although C. erythrophyllum has numerous traditional medicinal uses, there is limited scientific knowledge on the micromorphological structures and the associated exudate. Thus, this study aimed to characterize the micromorphological features of leaf and stembark secretory apparatus of C. erythrophyllum, using light and electron microscopy. Furthermore, a histo-phytochemical analysis was conducted to determine the presence and localization of phytometabolites within the trichomes and exudate. The antioxidant, antibacterial, apoptotic and cytotoxic potential of the leaf and stembark extracts were also evaluated. The micromorphological analysis identified the presence of peltate scales and non- glandular trichomes across surfaces. Peltate scales were comprised of a sunken basal cell, bicellular stalk, and a multicellular head. Head cell count appeared to increase upon leaf maturation. The granulocrine pathway was identified as a possible mode of secretion for C. erythrophyllum due to the extensive presence of vesicles, vacuoles, and electron dense material within the peltate scales. Preliminary histo-phytochemical analyses revealed the presence of carbohydrates, sterols, lipids, phenolic compounds, total proteins, alkaloids, and essential oils. Thin-layer chromatography allowed for the visualization of 36 compound classes while gas chromatography-mass spectrometry showed 266 compounds present. Fourier-transform infrared spectroscopy analysis confirmed the presence of phenols, alkenes, amines, alcohols, and esters among many. The antioxidant ability of the generated extracts were evaluated using the 2,2- diphenyl-1-picryl-hydrazyl-hydrate antioxidant assay and Ferric Reducing Antioxidant Power assay. A positive correlation between % inhibition and extract concentrations, was noted in both. In both instances, the methanol stembark extracts performed the best, (Leaf- 5,2866 and Stembark- 4,2866 μg/mL). Furthermore, the results obtained from the total flavonoid assay correlated with the trend observed through the total phenolic assay, whereby methanolic extracts yielded most promising results. Additionally, this study aimed to generate silver nanoparticles using crude extracts. A novel protocol for the synthesis of silver nanoparticles (AgNPs) using the leaf and stembark extracts of C. erythrophyllum was established. The generated AgNPs were characterized and evaluated for its potential antibacterial activity. Methanolic extracts inhibited the growth of Pseudomonas aeruginosa, Bacillus subtilis, Methicillin Resistant Staphylococcus aureus, and Staphylococcus aureus. Lastly, the generated crude extracts displayed promising results when evaluated for their cytotoxic and apoptotic abilities however upon nanoencapsulation the cytotoxic and apoptotic capabilities increased significantly. In correlation with the above, the AgNPs appeared to intensify the overall inhibition activity. Based on the findings of the study, Combretum erythrophyllum has a reservoir of unexplored allopathic potential which could revolutionize the medicinal world.