The therapeutic trial was conducted from December 2018 to May 2019 to compare the therapeutic efficacy of different drug regimens in the treatment of impactive and spasmodic colic in donkeys in Gondar, Northwest Ethiopia. Twenty-five purposively selected donkeys were used in this study. Ten of them were showing suspected clinical signs of impactive colic and the remaining ten were with spasmodic colic. The rest five donkeys were kept as control group. For this trial, each disease category was again grouped into two subgroups. The first sub-group in group A with suspected spasmodic colic was treated with ivermectin and, the second sub-group was treated with fenbendazole. Similarly, the first subgroup in group B with suspected impactive colic was treated with meloxicam and the remaining subgroup was treated with hyoscine butyl bromide. Most vital parameters were recorded before and after treatment of colicky donkeys. Feces and blood samples were collected and examined pre and post treatment from each donkey. Donkeys treated with ivermectin subcutaneously have 97.3% fecal egg count reduction percentage, whereas donkeys treated with fenbendazole orally have fecal egg count reduction percentage of 79.85%. Donkeys treated with meloxicam, most of the clinical signs disappear within 24 hours of time after treatment. Subcutaneous administration of ivermectin was effective for the treatment of spasmodic colic due to Strongyle infestation in donkeys. Therefore, field veterinarians should practice subcutaneous administration of ivermectin and intramuscular administration of meloxicam for effective treatment of spasmodic and impactive colic in donkeys, respectively.