The study evaluated the therapeutic efficacy of buparvaquone and oxytetracycline with and without antioxidant adjunctive therapy in small ruminants affected with theileriosis. The investigation was conducted at the Veterinary Clinical Complex, Veterinary College and Research Institute, Tirunelveli, from August 2024 to September 2025. Theileriosis-positive animals were randomly allocated into five groups (n = 6 each): Group I (buparvaquone alone), Group II (buparvaquone with vitamin E and selenium), Group III (oxytetracycline alone), Group IV (oxytetracycline with vitamin E and selenium), and Group V (healthy control). Clinical parameters were recorded on days 0, 3, and 9. Haematological indices, serum biochemical profiles, and oxidative stress markers were analysed. Data were subjected to one-way ANOVA, with P ≤ 0.05 considered statistically significant. All treated groups showed progressive clinical improvement from day 3 to day 9, with Group II demonstrating the most rapid and consistent recovery. Rectal temperature, heart rate, and respiratory rate declined significantly in all treated groups (P ≤ 0.05), and superficial lymph node enlargement resolved by day 9. Anaemia evident on day 0, characterized by reduced haemoglobin, packed cell volume, and total erythrocyte count, improved significantly by day 9, with Group II attaining values closest to normal. Differential leukocyte counts also normalized following treatment. Biochemical analysis indicated hepatic involvement on day 0, with elevated aspartate transaminase, alkaline phosphatase, and bilirubin concentrations, which declined significantly after therapy (P ≤ 0.05). Hypoproteinaemia and hypoalbuminaemia showed marked improvement, particularly in Group II, and blood urea nitrogen levels decreased significantly. Malondialdehyde levels were significantly elevated initially, while superoxide dismutase and glutathione peroxidase activities increased significantly by day 9, with maximum improvement in Group II. The study concludes that both buparvaquone and oxytetracycline are effective for treating small ruminant theileriosis, and adjunctive antioxidant supplementation significantly enhances therapeutic response, with buparvaquone plus antioxidants showing superior overall recovery.