Agarista salicifolia is the wild tree and has been used as important medicinal plants in South Ethiopia since a long time ago. The aim of this work was to carry out a chemical analysis focusing on secondary metabolites, particularly phenolic compounds, which have several roles in the plant physiological processes and have demonstrated significant capacity in the prevention of human health diseases. Phenolic acids, flavonols, flavan-3-ols, and dihydrochalcones were characterized and quantified using ultra high-performance liquid chromatography coupled with diode array and electrospray ionization mass spectrometric detection (LC-MS), FTIR, and UV-Visible spectroscopy techniques. After extraction with ethanol, compounds were characterized and quantified based on retention time, molecular ions, and the comparison with reference compounds. Six flavan-3-ols, four phenolic acids, five flavonols, and two dihydrochalcones were identified and quantified in the extract. Chlorogenic (279.23 ± 28.75 µg/g of dried leaf) acid, Quercetin-3-O-rhaminoside (97.24 ± 4.07 µg/g of dried leaf), and epicatechin (304. 57 ± 20.88 µg/g of dried leaf), were the most abundant phenolic acid, flavonol, and flavanols, respectively. This is the first study on the phenolic composition of A. salicifolia, highlighting the importance of these natural products as a source of medicinal applications in pharmaceutical industries by herbal drug manufacturers.