Background:Metronidazole is used for the treatment of trichomoniasis. However, a growing number ofTrichomonas vaginalis(T. vaginalis) isolates are now resistant, which is an urgent issue to search for new alternatives. Worldwide marine pharmacy confirms the enormous potential of sea species as a source of novel pharmaceuticals.Objective:This study aimed to investigate the anti-T. vaginalisactivities of ethanolic extracts of Red Sea marine resources, soft corals;Sarcophyton glaucumandLitophyton arboreumand methanolic extracts of Red Sea brown algae;Liagora farinosa, Colpomenia sinuosa, Hydroclathrus clathratus,andSargassum graminifolium, as well as sea cucumber (Holothuria fuscocinerea) and sea urchin (Echinometra mathaei).T. vaginalisgrowth inhibition was determined using 2 concentrations for each marine extract 10 and 100 µg/ml in comparison to media control. Drugs that showed good initial activity were further tested to calculate their IC50 in comparison to metronidazole. The ultrastructural impact of the more effective extracts was further assessed.Results:H. clathratus,L. farinose, sea urchinE. mathaeiand sea cucumberH. fuscocinereareduced the growth ofT. vaginaliseffectively and showed high activity with IC50 of 0.985±0.08, 0.949±0.04, 0.845±0.09 and 0.798±µg/ml±SD, respectively. Concerning microscopic analysis, marine extract and metronidazole-treated cells presented similar morphological changes. The nuclear membrane was damaged, the nuclei were dissolved, the rough endoplasmic reticulum was widened, and the chromatin was accumulated. In the cytoplasm, numerous autophagic vacuoles appeared, the organelles were disintegrated, the flagella were internalized and hydrogenosomes with altered morphologies were observed. The cell membrane was partially damaged, with cytoplasmic leakage and cell disintegration.Conclusion:This study describes the report on the activity and morphological changes induced by Egyptian Red Sea marine resources againstT. vaginalis. The results obtained herein presented new opportunitiess. Further, bio-guided fractionation and isolation of active compounds are needed.