Aquaporins (AQPs) are transmembrane channels essential for water, energy, and redox homeostasis, with proven involvement in a variety of pathophysiological conditions such as edema, glaucoma, nephrogenic diabetes insipidus, oxidative stress, sepsis, cancer, and metabolic dysfunctions. The 13 AQPs present in humans are widely distributed in all body districts, drawing cell lineage-specific expression patterns closely related to cell native functions. Compelling evidence indicates that AQPs are proteins with great potential as biomarkers and targets for therapeutic intervention. Aquaporin-9 (AQP9) is the most expressed in the liver, with implications in general metabolic and redox balance due to its aquaglyceroporin and peroxiporin activities, facilitating glycerol and hydrogen peroxide (HO) diffusion across membranes. AQP9 is also expressed in other tissues, and their altered expression is described in several human diseases, such as liver injury, inflammation, cancer, infertility, and immune disorders. The present review compiles the current knowledge of AQP9 implication in diseases and highlights its potential as a new biomarker for diagnosis and prognosis in clinical medicine.