Onchocerciasis is a disease caused by a parasitic nematode Onchocerca volvulus in human.  Ivermectin who is the main drug recommended for the treatment of this disease is only effective against the microfilarial stage of the parasite. Reports of emergence of parasite resistance to ivermectin have complicated onchocerciasis treatment and require to discover novel drugs. The objective of the present study was to investigate in vitro anthelmintic properties against the cattle filarial parasite Onchocerca ochengi, a model closely related to Onchocerca volvulus; and evaluate the toxicity (in vivo) of local medicinal plant Vernonia perrottetii. This plant is used as alternative medicine in the treatment of human onchocerciasis in central and coastal regions of Cameroon. Fifteen crude extracts were prepared from various parts of V. perrottetii using three organic solvents (70% ethanol, methanol, methylene chloride) and distilled water. The nematocidal activity was evaluated on adult worms of O. ochengi, worm viability was assessed biochemically using the dimethylthiazol (MTT) formazan assay. Oral toxicity of the promising extract was investigated in mice. The ethanolic extracts of the leaves and roots of V. perrottetii recorded the highest activities against adult male worms (LC50 of 29.80 μg/mL for leaves and 39.36 μg/mL for root). By contrast, the methanol and aqueous extracts of leaves and roots, of the plant as well as the mixture methylene chloride/methanol extracts. For acute treatment, a single dose of 2000 mg/kg no induced critical behavioral changes or death. In sub- acute treatment, daily oral administration of hydro-ethanolic extracts of leaves at the dose of 250, 500 and 750 mg/kg revealed disturbances in the normal growth of animals as well as liver and kidney alterations. Phytochemical analysis of the active extracts revealed the presence of Polyphenols, tannins, saponins and flavonoids. This study revealed the anti-Onchocerca activities of V. perrottetii, indicating a possible new source for developing a phytomedicine or drug for the treatment of human onchocerciasis.