Dried litchi pulp has been used in traditional remedies in China for many years to treat various diseases, and the therapeutic activity has been, at least partly, attributed to the presence of bioactive polysaccharides. Polysaccharide-protein complexes from vacuum freeze-(VF), vacuum microwave-(VM) and heat pump (HP) dried litchi pulp, which were coded as LP-VF, LP-VM and LP-HP, were comparatively studied on the physicochemical and immunomodulatory properties. LP-HP had a predominance of galactose, while glucose was the major sugar component in LP-VF and LP-VM. Compared with LP-VF and LP-VM, LP-HP contained more aspartate and glutamic in binding protein. LP-HP also exhibited a stronger stimulatory effect on splenocyte proliferation at 200 μg/mL and triggered higher NO, TNF-α and IL-6 secretion from RAW264.7 macrophages. Different drying methods caused the difference in physicochemical properties of polysaccharide-protein complexes from dried litchi pulp, which resulted in significantly different immunomodulatory activity. HP drying appears to be the best method for preparing litchi pulp to improve its immunomodulatory properties.