Olinia rochetiana is one of the medicinal plants traditionally used in Ethiopia to treat various ailments, including wounds, snake bites, tuberculosis, and cancer. However, there is a lack of comprehensive investigation regarding the biological activities of the phytoconstituents extracted from its leaves. This study aims to isolate compounds and evaluate their in vitro antibacterial properties and DPPH radical scavenging activities, complemented by in silico molecular modeling. Thirteen compounds were identified using GC–MS from combined fractions 4–17. Ursolic acid (14), 5-hydroxy-4-methyl-5,6-dihydro-(2H)-pyran-2-one (15), hyperoside (16), and 4-O-β-d-glucopyranosylcaffeic acid (17) were purified using chromatographic techniques and characterized using 1D and 2D NMR spectral data and a thorough comparison with literature data. At 5 mg/mL, the inhibition zones (IZs) of isolated compounds ranged from 9.00 to 12.67 mm against all of the evaluated bacteria. Among all isolated compounds, compound 14 exhibited more inhibition against Streptococcus pyogenes with an inhibition zone of 12.67 mm, and compound 17 also exhibited potent inhibition activity against Staphylococcus aureus with an inhibition zone of 11.00 mm. Escherichia coli and Pseudomonas aeruginosa were better inhibited using compound 16 with IZs of 12.30 and 11.70 mm, respectively. The antibacterial activity of compound 16 against E. coli and P. aeruginosawas validated using in silico molecular docking studies against the target enzymes E. coli DNA gyrase B (−8.4 kcal/mol) and Pseudomonas quinolone signal A (−9.3 kcal/mol), respectively. At 62.5 μg/mL, the highest (89.2%) and the lowest (50.5%) DPPH radicals were scavenged by compounds 16 and 14, respectively. Compounds 14, 15, and 17 obey Lipinski’s rule of five, and none of the isolated compounds were predicted to be fatal if swallowed. These findings reinforce the traditional use of the plant as a remedy for various bacterial diseases. However, further in vivo studies are essential to assess the biological and toxicological properties of the isolated compounds.