Phaleria macrocarpa (Scheff.) Boerl. (Thymelaeaceae), usually referred to as God’s crown, Mahkota dewa, Pau, grows all year long in tropical countries, including Malaysia, Indonesia, Papua New Guinea, and Australia. It is traditionally used to treat haemorrhoids, stroke, heart disease, tumour, impotence, diabetes, allergies, kidney and liver disorders, migraine, acne, and skin ailments.

The purpose of this systematic review is to provide important insight on P. macrocarpa’s traditional use, toxicity, classification of compounds, and pharmacological activities, thus identifying the gap in scientific analysis and potential analytical opportunities for future directions on this herb.

The related data for this systematic review were collected from renowned online databases, namely Wiley Online Library, Web of Science, Springer Link, PubMed, Science Direct, Scopus, and Google scholar.

Around 48 compounds, including benzophenone, xanthonoids, norcucurbitacin derivatives, flavonoids, lignans, fatty acids and esters, phytosterols, aromatic acids, etc., were identified from different parts. These constituents and different solvent extracts using various identification techniques have been reported to show a broad range of pharmacological activities. Besides various traditional claims and pharmacological functions, scientific evidence on its ethnopharmacological aspects has been well-documented. Studies found that the plant demonstrates anti-diabetic, anti- oxidant, antimicrobial, anticancer, anti-hypercholesterolemia, and antihypertensive activities.

Despite various claims, there is still inadequate scientific evidence, particularly on P. macrocarpa’s benefit in the management of dysentery, asthma, skin diseases, and rheumatoid arthritis, necessitating future studies. There is also a need to test its pharmacokinetics and toxicological data on humans to verify its potential bioactive properties.