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Gastrointestinal parasitic nematodes cause important economic harm to animal health, seriously affecting the livestock industry. Worldwide, economic losses from nematodiasis is reported at more than USD 10 billion a year in anthelmintic treatments alone in 2013. In Mexico, the livestock industry has reported losses of about $8.902 million Mexican pesos in the zootechnical potential of ruminants that interfere in the profitability of livestock farms. So far, these diseases have been controlled by use of anthelmintic products (AH). In addition, improper use of AH contributes to the imbalance of the environment, as well as an ecotoxicological risk to soil, plants, aquifers and beneficial organisms. In this context, the search for alternative and sustainable complementary methods that reduce the need for use of synthetic products of chemical origin, for example natural derivatives of edible fungi with a nematicidal effect, is evident. The edible fungi Pleurotus spp. possesses nutraceutical and therapeutic properties including their use as anti-parasitic. In the present investigation, in vitro effects of compounds derived from Pleurotus spp. were assessed against various stages of the parasitic nematode Haemonchus contortus. Pleurotus ostreatus had higher nematicidal activity than P. eryngii. The "F" fraction of hydroalcoholic extract of P. ostreatus mycelium showed the highest nematicidal activity (25.29%) with respect to other fractions. FpMeOH and FMeOH fractions had the highest L4 mortality rate of 84.8 and 100, respectively at 24 and 72 h. The spent mushroom substrates (SMS) of P. djamor had biological activity against H. contortus in its egg stages and L3. Furthermore, such activity is possibly influenced by the composition and/or the type of substrate. EHA-SA11 was lethal against L3 exsheathed with a 45% mortality at 20 mg/ml at 72 h postexposure, but did not affect nematode eggs. In contrast, EHA-SA13 was the most effective against parasite eggs with 100% inhibition starting at 2.5 mg/ml that was determined at CL90= 625 μg/ml. The use of a "nutraceutical" food based on SMS of edible mushroom culture represents a potential method of prevention of nematode infections. Inglés