Antitheilerial resistance and treatment failure are growing international concerns. Against this backdrop, the first study aimed to compare the efficacy of Juglone (a naturally occurring naphthoquinone) and buparvaquone against bovine tropical theileriosis during natural infection. A total of 60 adult cattle (2-4 years) were selected and divided into five groups, comprising 15 animals each. The animals of Group-I were administered two doses of buparvaquone (BPQ) at a dose rate of 2.5mg/kg body weight intramuscular, 48 hours apart. The cattle of Group-II were administered with BPQ and oxytetracycline (OXY) at the dose rate of 2.5 mg/kg (two doses at 48-hour intervals) and 20 mg/kg intramuscular 3 doses at 48-hour intervals, respectively. While infected animals of Group-Ш were treated with Juglone (JUG) at a dose rate of 0.48 mg/kg IV on alternate days for 7 days. Whereas, Group-IV acted as a healthy control. The hemogram revealed normocytic normochromic anemia in infected animals. A significant decrease of neutrophils along with decrease of total leukocytes and lymphocytes was noticed in recovered animals from all treated groups (Group I to III). After 21 days, the results of the therapeutic trial showed the highest efficacy of Group II (BPQ+OXY) (93.3%; 14/15), followed by Group III (JUG) (73.3%) and Group I (BPQ) (66.7%; 10/15) groups, three weeks after treatment. It can be concluded that BPQ+OXY had the highest efficacy; whereas the efficacy of Juglone is also comparable, this can be used as an alternative treatment against tropical theileriosis.