Background: Roots from Glycyrrhiza glabra L. are known for their anti-inflammatory and antimicrobial properties. This study focuses on the growth inhibitory activity of G. glabra root extracts against some bacterial triggers of autoimmune inflammatory disease alone and in combination with conventional antibiotics. Methods: G. glabra root powder was extracted with solvents of varying polarity and screened for bacterial growth inhibition by disc diffusion assay. The minimum inhibitory concentration (MIC) was quantified by both liquid dilution and disc diffusion techniques. To screen for combinatorial effects, the G. glabra root extracts were combined with a range of conventional antibiotics and tested against each bacterium using liquid dilution assays. Where synergy was detected, the optimal ratios were determined using isobologram analysis. Toxicity was examined using an Artemia nauplii and HDF bioassays. Results: G. glabra root methanolic, aqueous and ethyl acetate extracts displayed antimicrobial activity against bacterial triggers of some autoimmune inflammatory diseases. The ethyl acetate extract was particularly potent, with MIC values <500 μg/mL against K. pneumoniae and A. baylyi. The aqueous extract was also a moderate inhibitor of A. baylyi. The methanolic extract had moderate inhibitory activity against all bacteria except P. aeruginosa. Of further note, the aqueous extract interacted synergistically in combination with chloramphenicol against K. pneumoniae (Σ FIC 0.49). All extracts were nontoxic in the Artemia and HDF toxicity assays, further indicating their potential for medicinal use. Conclusions: The G. glabra ethyl acetate root extract was a strong inhibitor of the growth of K. pneumoniae and A. baylyi and therefore have potential in the prevention and treatment of ankylosing spondylitis and multiple sclerosis. In addition, the aqueous root extract potentiated the inhibitory activity of chloramphenicol against a chloramphenicol resistant K. pneumoniae strain. Although the mechanisms of synergy are still unclear, compounds within the G. glabra root extracts may mimic the actions of resistance modifying agents. Isolation of these agents may be beneficial in antibiotic drug design against bacterial triggers of ankylosing spondylitis.