A wide variety of herbal remedies are used in traditional African medicine to treat inflammatory disorders, including some autoimmune diseases. Thirty-four extracts from 13 South African plant species traditionally used for the treatment of inflammation were investigated for their ability to control a microbial trigger for ankylosing spondylitis (Klebsiella pneumoniae). Twenty-six of the extracts (76.5%) inhibited the growth of K. pneumoniae. Methanol and water extracts of Ballota africana, Carpobrotus edulis leaves, Kigellia africana, Lippia javanica, Pelargonium fasiculata, Syzygium cordatum (including bark), Terminalia pruinoides and Terminalia sericea were effective K. pneumoniae inhibitors, with MIC values <1000 µg/ml. The roots of Tulbaghia violaceae and bark from Warburgia salutaris also demonstrated efficacy. The most potent extracts were examined by RP-HPLC and UV-Vis spectroscopy for the presence of resveratrol. Methanolic extracts of B. africana, C. edulis leaves, L. javanica, T. pruinoides and T. sericea, as well as aqueous B. africana, T. pruinoides and T. sericea extracts, displayed peaks with retention times and UV-Vis spectra consistent with the presence of resveratrol. Resveratrol was generally a minor component, indicating that resveratrol was not solely responsible for the anti-Klebsiella growth inhibitory properties. Plant extracts with K. pneumoniae inhibitory activity were either non-toxic, or of low toxicity in the Artemia (brine shrimp) nauplii bioassay. Their low toxicity and antibiotic bioactivity against K. pneumoniae indicate their potential for both preventing the onset of ankylosing spondylitis and minimising its symptoms once the disease is established.