Avian coccidiosis is an economically important disease in the poultry industry. In view of the disadvantages of anti-coccidial drugs in chickens, edible plants and their compounds are re-emerging as an alternative strategy to combat this disease. A previous publication reported that the edible plant B. pilosa showed promise for use against coccidiosis. Here, we first investigated into the anti-coccidial effects of B. pilosa. We found that B. pilosa at 100 ppm or more significantly suppressed E. tenella as evidenced by reduction in mortality rate, oocyst excretion and gut pathological severity in chickens and its minimum prophylactic duration was 3 days. Next, we explored the mode of action of anti-coccidial mechanism of B. pilosa. The E. tenella oocysts were not directly killed by B. pilosa; however, administration of the plant suppressed oocyst sporulation, sporozoite invasion, and schizonts in the life cycle of E. tenella. Besides, B. pilosa boosted T cell-mediated immunity. Finally, we characterized the related anti-coccidial phytochemicals and their mode of action. One of three potent polyynes present in B. pilsoa, Compound 1 (cytopiloyne), acted against coccidiosis in chickens in a similar manner to B. pilosa. These data illustrate the anti-coccidial potency and mechanism of B. pilosa and one of its active compounds, and provide a cornerstone for development of novel herbal remedies for avian coccidiosis.