Introduction: Pyrroloquinoline quinone (PQQ) is a redox cofactor with antioxidant and immunomodulating actions implicated in protection of mitochondria and modulation of inflammation pathways. Oxidative stress is centrally involved in the onset of rheumatic diseases, such as RA, thus PQQ may be considered as a candidate for new therapeutic strategies. Objective: This article is aimed to objectively and critically analyse the scientific evidence available about PQQ in rheumatic diseases. Methods: A systematic review was performed in the PubMed, Scielo and LILACS databases with no language restriction, including articles published from January 1965 to May 2024. Studies using in vivo and human samples published in English were only included, but separate examination of in vitro and animal model studies. Results: There is no clinical evidence for PQQ in patients with rheumatic diseases. PQQ at the preclinical level In one preclinical study, it was reported that PQQ could downregulate inflammatory cytokines and matrix-metalloproteinase expression in synovial fibroblasts and ameliorate arthritis progression in a collagen-induced arthritis mouse model (23). Conclusions: Although experimental models suggest PQQ shows promise, there is no clinical evidence that it benefits patients with rheumatic diseases. Its potential as a therapeutic target requires further validation using translational research and clinical trials.