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One of the strategies for developing novel pharmaceutical drugs is to use natural sources such as plants for therapeutic treatment. Plant extracts are a cocktail of compounds which act synergically and can improve treatment effectiveness, reduce therapeutic duration and resistance. The ethanolic extracts of leaves and seeds of Cucurbita pepo ovifera var ovifera from Sudano-Guinean and Sudano-Sahelian zones of Cameroon were evaluated on the cattle parasite nematode Onchocerca ochengi. Worms were incubated with different concentrations of the plant extracts in RPMI-1640 supplemented with streptomycin and gentamicin. Mortality at 37°C was monitored after 24, 48 and 72 h. Ivermectin was used as positive control and DMSO as negative. Plant extracts from the two ecological zones showed anthelminthic activities on O. ochengi after 72 h with LC50 varying from 20 to 1090 µg /mL. The highest antifilarial activity in Sudano-Guinean zone was obtained with leave extract of C. pepo ovifera (LC50 of 20 µg/mL), while highest antifilarial activity in Sudano-Sahelian zone was obtained with seed extracts of the plant with LC50 value of 17 µg/mL after 72 h. These results show that anthelmintic activity depends on the part of the plant and the ecological zones. Additionally, the plant is not toxic. These results on the ethanolic extracts of leaves and seeds of C. pepo ovifera var ovifera confirmed the use of this plant in traditional medicine in Cameroon to treat disease due to nematodes. The plants could be used as alternative anthelmintic to fight against Human and Bovine onchocerciasis.