Ectoparasites of rodents play significant roles in disease transmission to humans. Conventional poisoning potentially reduces the population densities of rodents, however, they may increase the ectoparasite loads on the surviving hosts. EP-1 has been shown to have anti-fertility effects on many rodent species, while ivermectin is effective in controlling ectoparasites. In this study, we examined the combined effects of EP-1 and ivermectin mixture (iEP-1) baits on rodents and their corresponding flea/tick loads. In males, the weight of testis, epididymis, and seminiferous vesicle were reduced to less than 33%, 25%, and 17%, respectively, compared to the control group following administration of iEP-1 for 7 days. The weight of the uterus increased by approximately 75%. After 5 days of iEP-1 intake, all ticks were killed, whereas 94% of fleas on mice died after 3 days of bait intake. In the field test near Beijing, the flea index was reduced by more than 90% after 7 days of iEP-1 bait delivery. In a field test in Inner Mongolia, the weights of testis, epididymis, and seminiferous vesicle were significantly reduced by 27%, 32%, and 57%, respectively, 2 weeks after iEP-1 bait delivery. Approximately 36% rodents exhibited obvious uterine oedema accompanied by a weight increase of about 150%. The flea index was reduced by over 90%. Our results indicated that iEP-1 is a promising treatment for reducing the abundance of both small rodents and their ectoparasites; this will be effective for managing rodent damage and transmission of rodent-borne diseases associated with fleas and ticks. © 2022 Society of Chemical Industry.