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Background/Purpose: <i>Hymenolepis nana</i> is globally distributed. <i>Leucaena leucocephala</i> has been studied as a treatment, including the nematodes and protozoa, but no research results are related to cestodes. Therefore, the aim of this study was to target <i>H. nana</i>. Methods: The natural components of <i>L. leucocephala</i> were isolated and added to <i>H. nana,</i> which was cultured in vitro, to observe changes in the mortality, motility, and morphology. BALB/c male mice infected with <i>H. nana</i> were treated with effective components of <i>L. leucocephala</i> for 10 days, and the changes were recorded. After the mice were sacrificed, the spleen weight was measured, and a primary culture was performed for the subsequent cytokine and chemokine testing. Results: The experiment found that 13²-hydroxy-(13²-S)-pheophytin a and aristophyll-C have clear cestocidal effects in vitro. 13²-hydroxy-(13²-S)-pheophytin a has been shown to be effective at reducing parasite populations and eliciting host immune responses in vivo. IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, MCP-1, IFN-γ, TNF-α, MIP-1α, and GM-CSF in 13²-hydroxy-(13²-S)-pheophytin a were significantly increased after stimulation, while IL-1α, IL-1β, IL-3, IL-12p70, and RANTES were unchanged. Conclusions: The investigation shows that components of <i>L. leucocephala</i> have actual cestocidal activity against <i>H. nana</i>.