Propolis, a resinous substance, is collected from plants and processed by honeybees to seal holes and cracks in beehives, protecting them from microbial infection. Based on the plant source and geographical location, propolis is categorized into seven groups. Of these, Pacific propolis, found in the Pacific islands, originates from Macaranga spp. and is, therefore, known as Macaranga-type Pacific propolis. Okinawa propolis and Taiwanese propolis, which are both Macaranga-type propolis, are rich in prenylated flavonoids from the same botanical source, Macaranga tanarius, and are used locally as traditional remedies. They are reported to have a wide range of pharmacological benefits, including antioxidant, anti-inflammation, antimicrobial, anticancer, antidiabetic, anti-Alzheimer's, anti-melanogenic, and longevity-extending effects. However, not much is known about their mode of action, and recently, the extract of Okinawa propolis and its major prenylated flavonoids were found to selectively inhibit the oncogenic kinase, p21-activated kinase 1 (PAK1). PAK1 enables cross-talking among several signaling pathways, causing many diseases/disorders. The existing results reviewed here support the use of Macaranga-type Pacific propolis for the effective development of safe herbal drugs and functional foods. Furthermore, its mode of action by modulating PAK1 can be explored, and the geographical and seasonal effects on its chemistry and biology, and its pharmacokinetics and toxicology should be studied as well.