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Endometriosis is a chronic inflammatory gynecologic condition among women of reproductive age causing a plethora of symptoms that significantly affect their quality of life and mental health. Recent literature reports mounting evidence for several inflammation-mediated pathways for endometriosis pathogenesis, where elevated levels of proinflammatory factors, such as intercellular adhesion molecule 1, tumor necrosis factor-alpha, and nuclear factor kappa B have been established. Simultaneously, the prevalent clinical use of H1-antihistamines for other pathologies along with active research into its action pathways has led to our current understanding that H1-antihistamines counteract several inflammation mediators, including intercellular adhesion molecule 1, tumor necrosis factor-alpha, and nuclear factor kappa B. Although a wide range of existing drug-based endometriosis managements act via the estrogen-dependent pathways, along with some newer ones attempting to use antagonists of targeted inflammation-modulating factors, investigations into the direct use of H1-antihistamines in the context of endometriosis are currently lacking. In this brief perspective opinion essay, correlative evidence has been placed forward that points toward a potential avenue of H1-antihistamines for endometriosis management, and some ideas have been highlighted for future research considerations., (© 2023 The Authors.)