Gastrointestinal helminths significantly impact equine health, performance, and welfare. The heavy reliance on anthelmintics for parasite control has raised growing concerns about drug resistance. From October 2023 to April 2024, a cross-sectional study was conducted at Asella and Shashemene to estimate helminth prevalence, assessed risk factors, and evaluated anthelmintic efficacy in equines. Standard parasitological methods were applied to 382 samples to detect parasite eggs or larvae. The fecal egg count reduction test (FECRT) was used to assess anthelmintic efficacy on 180 naturally infected horses (n=90) and donkeys (n=90). At each area, 90 helminth-positive animals, with egg count ≥500 EPG, were assigned to three treatment groups: Fenbendazole, Ivermectin, and a non-treated control. Fecal egg counts were made measured on the day of treatment and 14 days later. The overall prevalence of gastrointestinal helminths was 72%. Parasites identified included Strongylus species (63.87%), Strongyloides westeri (4.71%), Oxyuris equi (4.45%), Parascaris equorum (5.5%), Fasciola hepatica (4.97%), Gastrodiscus species (3.1%), Dicrocillium species (1.3%), Schistosoma species (1.1%), and Anoplocephala perfoliata (5.2%). Parasite burden analysis revealed that most of the animals had light (51.0%), or moderate (38.2%) infections, while 10.7% of they were heavily infected. Prevalence was varied significantly with animal species, age, and study area. The anthelmintic efficacy study showed resistance to Fenbendazole in horses, while parasites in donkeys remained susceptible to both Fenbendazole and Ivermectin. The findings underscore the importance of GIT parasite control in equine and careful use of anthelmintics to manage resistance and maintain effective parasite control.