Background: As secretory phospholipase A2 (sPLA2) was shown to be elevated in patients who progress to severe dengue, it would be important to evaluate the usefulness of therapeutics that inhibit sPLA2 enzymes to prevent progression to severe dengue. Methods: Aqueous and butanol extracts of Tragia hispida, Justicia adathoda and tubers of Cyperus rotundus were screened for the presence of potential sPLA2 inhibitors using a commercial assay measuring sPLA2 activity. Results: Both the aqueous (THA) and butanol extracts (THB) of Tragia hispida had sPLA2 inhibition levels comparable to the levels seen with the commercial sPLA2 inhibitor CAY10590. THB at concentrations of 0.1 µg/µL and 0.2 µg/µL, significantly reduced the sPLA2 activity (p<0.0001) in the sera of dengue patients and the inhibitory activity was significantly higher (p<0.0001) than of CAY10590. Thin layer chromatography of THB showed that it was likely to contain a mixture of flavonoid and phenolic compounds. HPLC displayed peaks at 3.207 min (λmax 222 nm, 272 nm) and 7.972 min (λmax 224 nm, 272 nm) which were most likely to represent phenolics and peaks at 11.883 min (λmax 276 nm, 366 nm) and 16.898 min ( λmax 254 nm, 370 nm) which were most likely to represent flavonoids. Conclusions: T. hispida aqueous and butanol soluble fraction had potent sPLA2 inhibitory activities, which should be further explored for their potential to be used for treatment of dengue.