The increasing resistance of head lice Pediculus humanus capitis to many drugs has highlighted the need for new alternatives to control head lice in adults. The effect of two types of extracts (aqueous and alcoholic) of Citrullus colocynthis fruit on adult lice was tested in vitro. The results showed that the alcoholic extract with a concentration of 20% showed similar efficacy in killing adult lice to that of Natroba 9% w/ w, with values ranging between 87% to 98% within 18 minutes, followed by a 20% aqueous extract with a 44% to 79% death rate. A 10% concentration of both types of extracts had moderate lethality for lice, while a 5% concentration did not show strong lethality for adult lice. These results revealed significant differences between the control group and those treated with alcoholic and aqueous extract concentrations of C. colocynthis fruits at the probability level p ≤ 0.05.