Kyllinga polyphylla Willd. ex Kunth. (KP) is a wild herb commonly distributed in the Mekong Delta, Vietnam. Tis study wascarried out to evaluate the antibacterial and antioxidant activities and acute toxicity of KP before conducting studies at the in vivolevel. All parts of KP had the free radical scavenging capacity of DPPH, in which the root methanol extract had the best antioxidantcapacity (EC 50 � 9.54 ± 0.37 μg/mL). Most of the extracts had a wide range of antibacterial spectra. Te methanol and ethanolextracts (200 mg/mL) have ability to resist eight common bacterial strains (including Staphylococcus aureus, Listeria innocua,Bacillus subtilis, Bacillus cereus, Escherichia coli, Salmonella sp., Pseudomonas aeruginosa, and Enterococcus faecalis), which isequivalent to the antibacterial activity of amoxicillin and tetracycline at a concentration of 1 mg/mL. KP extracts did not causedeath at a dose of 5000 mg/kg body weight and did not signifcantly change the biochemical, hematological, as well as histologicalstructures of internal organs in toxicity-tested mice in comparison with the control. Te research results showed that KP should bemore interested in research that supports disease treatment, synthetic extraction of antibiotics, or other in vivo studies.