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<i>Nosema ceranae</i> (Opisthosporidia: Microsporidia) is an emergent intracellular parasite of the European honey bee (<i>Apis mellifera</i>) and causes serious <i>Nosema</i> disease which has been associated with worldwide honey bee colony losses. The only registered treatment for <i>Nosema</i> disease is fumagillin-b, and this has raised concerns about resistance and off-target effects. Fumagillin-B is banned from use in honey bee colonies in many countries, particularly in Europe. As a result, there is an urgent need for new and effective therapeutic options to treat <i>Nosema</i> disease in honey bees. An RNA interference (RNAi)-based approach can be a potent strategy for controlling diseases in honey bees. We explored the therapeutic potential of silencing the sequences of two <i>N. ceranae</i> encoded spore wall protein (SWP) genes by means of the RNAi-based methodology. Our study revealed that the oral ingestion of dsRNAs corresponding to SWP8 and SWP12 used separately or in combination could lead to a significant reduction in spore load, improve immunity, and extend the lifespan of <i>N. ceranae</i>-infected bees. The results from the work completed here enhance our understanding of honey bee host responses to microsporidia infection and highlight that RNAi-based therapeutics are a promising treatment for honey bee diseases.