Yeast Glucan Particles (YGPs), emerging drug carriers, exhibit specific uptake by macrophages, aiding targeted imaging and drug delivery to inflammation and tumors. This review outlines YGP application in oral targeted delivery, covering yeast cell structure, preparation, drug encapsulation, and validation of macrophage recognition. Inspiring cases highlight yeast cells’ promising applications. Challenges and future prospects for YGPs are emphasized. YGPs act as both “armor” and “compass” for targeted drug transport, offering a novel approach for oral delivery of anti-inflammatory and anti-tumor drugs, potentially extending to macrophage-related diseases’ targeted therapy.