Presently, no effective anthelmintic drugs have been used to treat and control paramphistomosis, a severe disease of ruminants. In this study, we have investigated the in vitro anthelmintic effect of the leaves of Terminalia catappa L. crude extract (TcCE) and albendazole (ABZ) on adult Fischoederius cobboldi after incubating the flukes in RPMI-1640 medium containing the TcCE at various doses and times. The TcCE-treated flukes at all dosages exhibited rapid decrease of motility, and the relative motility (RM) values were decreased sharply from start to 3 h. Worms were killed after 6 and 12 h of treatment with 1000, 1500 and 2000 µg mL−1 as well as 500 µg mL−1 of TcCE, respectively. By light microscopy examination, the flukes exhibited the earliest alteration in a limited area of the tegument. At scanning electron microscopy level, the flukes’ tegument showed similar sequence of morphological alterations after treatment with ABZ and TcCE that consisted of swelling of ridges and folds, followed by blebbing and rupturing of the blebs, leading to the erosion, lesion and disruption of the tegument. Hence, in vivo studies should be performed to examine whether the TcCE may serve as a powerful anthelmintic drug for treatment of paramphistomosis.