Eurytrema coelomaticum are trematodes that parasitize cattle, buffaloes, goats, sheep, and camelids, and, accidentally, humans and cats. The affected animal usually has a subclinical pancreatic disease, but the damage caused to health and animal production is underestimated. Currently, praziquantel is the unique drug proven effective against this parasite, but no formulations containing this drug are available for ruminants in Brazilian market. The objective of the present study was to separately evaluate in vitro anthelmintic activity of praziquantel (PZQ) and nitazoxanide (NTZ) against E. coelomaticum by assessing motility after 3, 12, and, 15 hours of incubation and subsequent histopathological examination of the parasites. E. coelomaticum specimens were obtained from the pancreas of naturally infected cattle, collected from animals slaughtered in the city of Concordia-SC, Brazil. The specimens were incubated in plates with a culture medium (n = 60 per group), with 80µg/ml of PZQ (positive control group), or 61,5µg/ml of NTZ (treated group), or UNT (untreated control). After 12 hours of incubation all parasites of the NTZ and PZQ groups were motionless or dead, while in the negative control group, 91.67% (55/60) presented normal motility after 15 hours of incubation (P < 0.001). Histopathological examination showed severe damage in vitellogenic gland, intestine, parenchyma, integument, and testicle in both treated and positive control groups. It was concluded that PZQ and NTZ showed in vitro anthelmintic action against the parasite Eurytrema coelomaticum, as they caused significant lesions in the evaluated organs and reduced the parasite’s motility.