Syzygium cumini (Java plum) and Syzygium aromaticum (clove) are two species of the genus Syzygium (Myrtaceae), comprising 1200–1800 species. Both hold significant ethnopharmacological importance in traditional medicine systems across Asia, Africa, and Oceania. This comprehensive review updates the current knowledge on the traditional uses and pharmacological activities of S. cumini and S. aromaticum, with additional references to other Syzygium species (S. aqueum, S. malaccense, and S. samarangense) where relevant data exist. The review integrates information from in vitro and in vivo experiments, clinical trials, and formulation developments (2013-2026). The identified pharmacological properties are comprehensive, encompassing antioxidant, antibacterial, anti-inflammatory, cytotoxic, antidiabetic, anticholinesterase, and antiparasitic effects. These bioactivities are attributed to a diverse array of phytochemicals, such as flavonoids, phenolic acids, tannins, and essential oil components like eugenol. Recent advances in nanoencapsulation and biopolymer-based formulations have shown promising physicochemical properties and biological activity, supporting further investigation for wound healing and inflammatory conditions; however, enhanced bioavailability remains to be established. This review highlights S. cumini and S. aromaticum as a vital reservoir of bioactive compounds for evidence-based phytotherapy and underscores the need for further clinical research to translate these findings into effective therapeutic strategies.