Dennettia tripetala a Nigerian medicinal plant widely employed in the management of oxidative stress related diseases and infections was investigated for its active constituents. A DPPH (1,1-diphenyl-2-picrylhydrazine) guided fractionation was used to target and isolate the antioxidant constituents of the ethyl acetate solvent fraction of a 20% aqueous methanol leaf extract. Two flavonoid glycosides were isolated and identified by spectral data (1H, and 13C NMR, along with ESI-TOF-MS spectrometry) as: quercetin-3-O-arabinofuranoside, avicularin (1) and vitexin-2'’-O-rhamnoside (2). In the qualitative antioxidant assay, the compounds instantly bleached the DPPH purple colour indicating free radical scavenging potential (antioxidant activity). In the micro-well dilution assay, Compound (1) was the most active with MIC values of 0.081 mg/mL against Staphylococcus aureus NCTC 6571 and 2.50 mg/mL against Escherichia coli NCTC 8196 compared to the standard drug streptomycin which had MICs of 0.039 mg/mL and 0.156 mg/mL respectively against the two organisms. None of the compounds was able to inhibit the growth of the fungi strain used at the tested concentrations. Isolation of these antioxidant and antimicrobial compounds could provide rationale for the ethnomedicinal use of this plant in traditional medicine in the management of the oxidative stress related diseases and infections.