Broussonetia papyrifera panicles are rich in polysaccharides and other bioactive components. In this study, RAW264.7 macrophages were used as a model to evaluate the immunomodulatory effects of deproteinized polysaccharide from Broussonetia papyrifera panicles (BBP), and an oxidized low-density lipoprotein (ox-LDL)-induced foam cell model was established to investigate its effects on lipid deposition, oxidative stress, and inflammatory responses. The results showed that BBP exhibited no obvious cytotoxicity toward RAW264.7 cells at concentrations ranging from 0 to 1000 μg·mL-1. BBP treatment increased the secretion levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO) in a concentration-dependent manner, while enhancing cellular phagocytosis and pinocytosis. The phagocytic activity reached the highest level at 1000 μg·mL-1 BBP, which was 349.34% of that in the control group. In the ox-LDL-induced foam cell model, BBP decreased the cholesteryl ester/total cholesterol (CE/TC) ratio from 52.97% in the model group to 40.50%, while reducing the reactive oxygen species (ROS) level from 97.14 to 54.85 and the malondialdehyde (MDA) content from 1.88 to 0.89 nmol·mg-1. In addition, BBP treatment markedly decreased the secretion levels of TNF-α, interleukin-1β (IL-1β), and IL-6 in foam cells. In conclusion, BBP can modulate the immune function of RAW264.7 macrophages and alleviate lipid deposition and oxidative stress under ox-LDL-induced conditions, providing cellular evidence for further investigation of the functional properties and resource utilization of polysaccharides from Broussonetia papyrifera panicles.