The demand for medicinal plants is on a rise due to their affordability, accessibility and relatively non-toxic nature. Combretum molle (Combretaceae) is used in African traditional medicine to treat a number of diseases. This study aimed to screen the phytochemical composition of the hexane, chloroform and methanol extracts of C. molle leaves and stems using qualitative phytochemical screening. Additionally, the study aimed to identify the functional phytochemical groups, determine the elemental composition and provide a fluorescence characterization of the powdered leaves and stems by performing Fourier transform infrared spectroscopy (FTIR), energy-dispersive X-ray (EDX) microanalyses and fluorescence microscopy. Phytochemical screening revealed the presence of alkaloids, flavonoids, phenolic compounds, polyphenols, terpenoids, tannins, coumarins, saponins, phytosterols, gums, mucilage, carbohydrates, amino acids and proteins within all leaf and stem extracts. Lipids and fixed oils were additionally present within the methanol extracts. FTIR demonstrated significant peaks in absorption frequency in the leaf at wavelengths of 3283.18, 2917.81, 1617.72, 1318.83, 1233.97, 1032.32 and 521.38 cm−1, and in the stem at 3318.91, 1619.25, 1317.13, 1032.68, 780.86 and 516.39 cm−1. These corresponded to the functional groups of chemical compounds including alcohols, phenols, primary amines, alkyl halides, alkanes and alkyl aryl ethers, corroborating the presence of the detected phytochemicals within the plant. EDX microanalyses showed the elemental composition of the powdered leaves (68.44% C, 26.72% O, 1.87% Ca, 0.96% Cl, 0.93% Mg, 0.71% K, 0.13% Na, 0.12 % Mn and 0.10% Rb) and stems (54.92% C, 42.86% O, 1.7% Ca, 0.43% Mg and 0.09% Mn). Fluorescence microscopy provided a characteristic evaluation of the plant in its powdered form and revealed distinct colour changes in the material when treated with various reagents and viewed under ultraviolet light. In conclusion, the phytochemical constituents of the leaves and stems of C. molle confirm the suitability of this species for use in traditional medicine. The findings from this study suggest the need to validate the use of C. molle in the development of modern medicines.