A library of 206 extracts from selected South African plants was screened <i>in vitro</i> against a panel of protozoan parasites, <i>Plasmodium falciparum, Trypanosoma brucei rhodesiense</i>, and <i>Leishmania donovani</i>. A CH₂Cl₂/MeOH (1 : 1) extract of <i>Abrus precatorius</i> L. ssp. <i>africanus</i> strongly inhibited <i>P. falciparum</i> (98 %), <i>T. b. rhodesiense</i> (100 %), and <i>L. donovani</i> (76 %) when tested at a concentration of 10.0 µg/mL. The active constituents were tracked by HPLC-based activity profiling and isolated by preparative and semipreparative RP-HPLC chromatography. Structures were established by HR-ESIMS, and 1D and 2D NMR (¹H, ¹³C, COSY, HMBC, HSQC, and NOE difference spectroscopy). Five compounds were obtained and identified as two isoflavan hydroquinones, abruquinone H (<b>1</b>) and abruquinone G (<b>2</b>), and three isoflavan quinones, abruquinone I (<b>3</b>), abruquinone B (<b>4</b>), and 7,8,3′'5′-tetramethoxyisoflavan-1′,4′-quinone (<b>5</b>). Compounds <b>1</b> and <b>3</b> were new natural products. The absolute configuration of compounds was determined by comparison of electronic circular dichroism spectra with calculated ECD data. Compounds <b>3</b> and <b>4</b> showed strong activity against <i>T. b. rhodesiense</i> (IC₅₀ values of 0.30 and 0.16 µM, respectively) and good selectivity (selectivity indices of 73.7 and 50.5, respectively).