The ethanol extract of A. phylicoides was investigated for its antioxidant activity using the DPPH scavenging method. The extract showed good antioxidant results with a EC50 value of 10.64 ± 0.0842 µ/ml. The extract was also tested for antibacterial activity against microorganisms (Staphylococcus aureus, Enterococus faecalis, Bacillus cereus, Bacillus subtilis, Bacillus pumilus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumonia) commonly known to pose a threat in the wellbeing of man. All tested microorganisms were significantly inhibited by the extract with the MIC values ranging from 3.13 µg/ml to 6.25 µg/ml. Folin-Ciocalteu’s reagent method was used to determine total phenolic content of dried and freshly prepared crude extract of A. phylicoides. Higher total phenolic content (28.28 ± 0.019 mg GAC/100g) and antioxidant activity (EC50, 10.64 ± 0.084 µg/ml) was observed in the dried extract compared to the fresh extract with a TPC value of 23.04 ± 0.003 mg GAC/100g and EC50 of 13.97 ± 0.066 µg/ml. Bioassay-guided fractionation of ethanolic extract from aerial parts of Athrixia phylicoides using silica and sephadex column chromatography led to the isolation of four known flavanoids, 5-hydroxy-6,7,8,3’,4’,5’-hexamethoxyflavon-3-ol (1), 3-0- demethyldigicitrin (2), 5,6,7,8,3’,4’-hexamethoxyflavone (3) and Quecertin (4). Due to the low yield, no further tests were done on compound 3. A DPPH-scavenging assay was performed to evaluate the antioxidant activity of the isolated compounds. All the tested compounds showed potent antioxidant activity with EC50 values ranging from 1.27 to 3.41 µg/ml. Compound 4 showed a higher antioxidant activity (EC50, 1.27 µg/ml) than vitamin C (EC50, 2.66 µg/ml) used as a control. The MIC values of the isolated compounds against tested microorganisms varied from 20 to more than 40 µg/ml. All the tested compounds showed no activity against S. aureus, B. pumilus, K. pneumonia and P. aeruginosa at the highest concentration tested (40 µg/ml). These compounds together with the extract were further analyzed by XTT assay on Vero cells. The extract showed a low toxicity effect on the cells at lower concentrations exhibiting EC50 value of 107.8 ± 0.129 µg/ml. Compound 4 showed minimal toxicity effect on the cells with a EC50 value of 81.38±0.331 µg/ml, compared to Compound 1 and 2 which exhibited EC50 values of 27.91 ± 0.181 µg/ml and 28.92 ± 0.118 µg/ml respectively. The results obtained from this study provide a clear rationale for the medicinal uses of Athrixia phylicoides.