As the spread of canine leishmaniasis (CanL) is increasing throughout the world, the need for effective agents to prevent its transmission has intensified. In this case report, an intact 1.5-year-old male French bulldog was presented for treatment of severe, sudden, and constant lameness on his right hindlimb, which had started approximately four months previously and was unresponsive to routine nonsteroidal anti-inflammatory drugs. A Neem oil-based product was sprayed three times a week on the dog’s coat for about fourteen months as the only prophylactic measure against CanL. The orthopedic examination revealed grade 3–4 lameness and marked atrophy of the thigh muscles with swollen and painful right stifle joint. The radiological investigation showed polyostotic periosteal proliferation at both hindlimbs. The diagnosis of CanL was established by examination of fine-needle aspiration of lymph nodes (left prescapular, right and left popliteal) and immunofluorescence antibody testing. A leishmanicidal therapeutic protocol was prescribed. Within ten days of starting the therapy, the dog was significantly less lame, and eight months later radiographic examination revealed complete regression of the bone lesions. Some owners resort to a naturalistic approach for CanL prevention, also using products that have not been clinically evaluated. Neem oil is thought to prevent sandfly bites in dogs. Some laboratory and field studies have identified Neem oil as a possible alternative herbal drug that is repellent to sandflies. However, the clinical, laboratory, and radiographic findings clearly show that the Neem oil spray formulation used in this case report was not an effective means of CanL prevention. There is no clinical evidence in support of Neem oil-based products for the protection of dogs against CanL transmission. As Neem oil has previously been shown to be somewhat volatile, this case report suggests that even though it is a very effective repellent against sandflies, in practice, its effect on the dogs’ coat was only short-lived.