Autoimmune diseases are a diverse group of diseases with multiple phases of progression. These are not generally adequately treated and there are currently no cures for any of these diseases. Instead, medical interventions aim to treat the symptoms (pain, inflammation, swelling, etc.) without addressing either the disease etiology or the multiple other phases of disease progression. Plants of the genus Syzygium are used traditionally for a myriad of therapeutic purposes, including uses as antibacterial, antifungal, antiprotozoal, antiviral, antidiarrheal, and antidiabetes drugs. Several species are also known for their analgesic, antiinflammatory, and anticancer activities. Many of these traditional uses are relevant to the various phases of autoimmune diseases. Therefore, Syzygium spp. extracts and essential oils have potential as pluripotent chemotherapies, targeting multiple phases of the autoimmune disease progression. A single extract may inhibit a microbial initiator of the disease, block the interaction between the antigen and the immune system, modulate the immune response if it is initiated, and inhibit the later phase inflammatory events, thereby lessening the symptoms. Furthermore, Syzygium spp. extracts often have high antioxidant capacities and may also prevent these diseases. Despite this, many Syzygium spp. extracts are yet to be examined for bioactivities against drug targets relevant to the autoimmune diseases. This study reviews the current literature in this field with the aim of highlighting the therapeutic potential of this genus and stimulating further studies.