Background <p><i>Trypanosoma evansi</i> is a common protozoal disease affecting livestock, involving camels, and results in considerable economic losses. The purpose of this research was to assess the efficacy of the terpenoids-enriched fraction of <i>Salvia officinalis</i> (<i>S. officinalis</i>) and the sesquiterpene lactones-enriched fraction of <i>Cichorium intybus</i> (<i>C. intybus</i>) against trypanosomiasis and the associated oxidative damage in liver and kidney of <i>Trypanosoma evansi (T. evansi)-</i>infected rats<i>.</i> A total of one hundred male rats were equally divided into five groups: Group A served as negative control. Group B received an intraperitoneal infection with <i>T. evansi</i> (1 × 10⁴ trypanosomes/rat). Group C was infected and treated intramuscularly with 7 mg/kg body weight of diminazene aceturate. Groups D and E were also infected with <i>T. evansi</i> and given 300 mg/kg body weight as a daily oral dose of <i>S. officinalis</i> terpenoids-enriched fraction and 200 mg/kg body weight of <i>C. intybus</i> sesquiterpene lactones-enriched fraction, respectively, for 1 month.</p> Results <p><i>T. evansi</i> infection induced an elevation in serum hepatic transaminases activity and urea level with hyperglobulinemia. Along with histopathological alterations in the liver and kidney, <i>T. evansi</i> significantly decreased glutathione peroxidase (GPx) activity and reduced glutathione (GSH) content, in addition to the elevation of malondialdehyde (MDA) content in both tissues. The administration of <i>S. officinalis</i> and <i>C. intybus</i> fractions markedly reduced the level of parasitemia and alleviated the biochemical alterations and oxidative damage induced by <i>T. evansi</i>.</p> Conclusion <p>The terpenoids-enriched fraction of <i>S. officinalis</i> and sesquiterpene lactones-enriched fraction of <i>C. intybus</i> display a remarkable anti-trypanosomal and antioxidant potentials and may be promising sources for novel trypanocidal agents.</p>