###### Abstract  
The high resistance evolution of protozoans to the existing antiparasitic drugs has necessitated the quest for novel and effective drugs against plasmodium and trypanosome parasites. As a result, this study aimed to assess the antiplasmodial and antitrypanosomal potentials of chloroform, ethyl acetate and ethanol leaf extracts of _Oedera genistifolia_. Standard biochemical procedures were explored for the plant extraction and gas chromatography-mass spectroscopy (GCMS) was used to identify the bioactive compounds in the crude extracts. The cytotoxic effects of the crude extracts were assessed against human cervix adenocarcinoma (HeLa cells) and their antiparasitic activities were investigated against _Plasmodium falciparum_ strain 3D7 and _Trypanosoma brucei brucei_. GCMS analyses of the crude extracts revealed the bioactive compounds that could be responsible for the biological activities. The extracts had no cytotoxic effect on HeLa cells and demonstrated good antiplasmodial activity (chloroform extract: IC\({}_{50}\) = 11.6 \(\upmu\)g mL\({}^{-1}\), ethyl acetate extract: IC\({}_{50}\) = 3.3 \(\upmu\)g mL\({}^{-1}\) and ethanol extract: IC\({}_{50}\) = 3.7 \(\upmu\)g mL\({}^{-1}\)). Likewise, they showed excellent antitrypanosomal activity with IC\({}_{50}\) = 0.5 \(\upmu\)g mL\({}^{-1}\) for chloroform and ethyl acetate extracts and IC\({}_{50}\) = 0.4 \(\upmu\)g mL\({}^{-1}\) for the ethanol extract. Findings from the present study indicated that O. _genistifolia_ could be a good source of strong antiplasmodial and antitrypanosomal agents. Oedera genistifolia; bioactive compounds; cytotoxicity; antiplasmodial; antitrypanosomal 20202  
long usage cannot be neglected and are coupled with other demerits such as high cost, drug failure and a high resistance rate. Consequently, these aforementioned reasons have underscored the unending and urgent need for the discovery and development of potent, cost-effective and innocuous antimalarial drugs [2; 3; 4]. African trypanosomiasis is a parasitic disease caused by _Trypanosoma brucei brucei_ which has affected the lives of about 48 million cattle and 60 million people worldwide [5; 6]. Regrettably, antitrypanosomal drugs are not economical and their side effects, as well as the rate at which a new strain of these parasites develops resistance to the existing drugs, have rather caused them to be ineffective [7]. Consequently, the search for safe and cheap therapeutic drugs from plant sources could be considered as an alternative. Nevertheless, some studies on the antitrypanosomal activity of plant extracts and plant derivatives have been recently documented [8; 9; 10]. Historically, plants and their derivatives have been reported to be the foundation for the discovery of leads used in the designing of drugs to treat various types of human diseases [2]. It is appraised that 66-85% of the world's population relies on folkloric herbs and the search for drugs derived from plants has been increasing in the last two decades [11; 12; 13; 14; 15; 16]. African medicinal plants are known to contain a large variety of bioactive compounds and extracts of these plants have been screened for various biological activities, in the pursuit for prospective novel therapeutic drugs against the different human and animal illnesses [17; 18]. Several plant bioactive compounds such as tannins, flavonoids, glycosides, alkaloids, anthraquinones and alkaloids have been labeled with antiplasmodial and antitrypanosomal activities [2]. _Oedera genistifolia_ (\"Klein Perdekaroo\") is a prickly shrublet that is grouped to the daisy family (Compositae or Asteraceae). They are usually found in the Southwestern Cape, South Africa (Namaqualand to Grahamstown) and mostly present on the lower north-facing slopes, especially on rocky clay and shale-based soils. The aqueous leaf extract of _O. genistifolia_ has been explored for green silver nanoparticles and their antibacterial activity has been reported in our previous studies [19].