Asian small-clawed otters (ASCO; Aonyx cinereus) are a popular species of otter housed in zoological institutions. A common health challenge in this species is the development of uroliths, which may have a dietary origin. Feeding recommendations for ASCO are largely based on the nutrient requirements of domestic carnivore models. Using otter-specific feeding ecology may allow for further refinement of these nutrient recommendations. This study aimed to assess if a naturalistic diet of crustaceans, mollusks, and fish could control the development of uroliths in ASCO. Baseline data were collected on 10 ASCO (five males and five females) of different ages and repeated 2 years after the treatment diet was introduced. Blood and urine parameters, as well as the size of nephroliths based on radiographic images, were recorded. The treatment diet was higher in protein and lower in calcium than the nontreatment diet and did not contain any kibble. During the 2-year treatment trial, blood globulin, glucose, and sodium increased and albumin decreased. Glucosuria and leukocyturia significantly decreased. There were no significant changes in urolith size over the 2 years, and animals without nephroliths at the beginning of the study remained urolith free. The development of nephroliths was significantly reduced during the treatment compared with the year prior. Although interpretation is limited by the methods used, a naturalist diet may have a beneficial impact in the development of uroliths in ASCO.