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Some evidence indicated that human babesiosis caused by <i>Babesia duncani</i> has spread widely in North America. However, current therapeutic regimens (atovaquone + azithromycin) for human babesiosis are suboptimal with frequent recrudescence and side effects, and furthermore, there is no specific treatment for human babesiosis caused by <i>B. duncani</i>. Here, we screened 97 essential oils and identified 10 essential oils (garlic, black pepper, tarragon, palo santo, coconut, pine, meditation, cajeput, moringa, and stress relief) at a low concentration (0.001%; <i>v</i>/<i>v</i>) that showed good inhibitory activity against <i>B. duncani</i> in the hamster red blood cell culture model. Among them, garlic oil and black pepper oil performed best, as well as their potential active ingredients diallyl disulfide (DADS) and β-caryophyllene (BCP), respectively. Interestingly, further subculture study indicated that <i>B. duncani</i> could relapse after treatment with current therapeutic drugs atovaquone or azithromycin even at high concentrations. In contrast, the combination of garlic oil or DADS and azithromycin showed eradication of <i>B. duncani</i> at low concentrations without regrowth. These results are encouraging and suggest that the garlic-derived sulfur compound DADS and β-caryophyllene (BCP) may be promising drug candidates for evaluation of their ability to cure persistent <i>B. duncani</i> infections in the future.