Background/Objectives: Fisetin (3,3′,4′,7-tetrahydroxyflavone) is a naturally occurring flavonol present in strawberries, apples, grapes, onions, cucumbers, and other plant sources. It has attracted considerable interest because of its antioxidant, anti-inflammatory, antimicrobial, anticancer, neuroprotective, cardioprotective, and senolytic properties. This review comprehensively evaluated the pharmacological activities, mechanisms of action, translational challenges, and global research trends associated with fisetin. Methods: A comprehensive literature review was conducted to synthesise evidence on the traditional uses, pharmacological properties, molecular mechanisms, and therapeutic applications of fisetin. Bibliometric analysis of publications from 2005 to 2024 was performed using the Web of Science Core Collection. A total of 664 records were retrieved using the keywords “fisetin” and “3,3′,4′,7-tetrahydroxyflavone”. Following refinement using Bibliometrix (version 5.0) and the Biblioshiny interface in RStudio, 658 publications were included in the final analysis. Results: Fisetin exhibited diverse biological activities through modulation of oxidative stress, inflammation, apoptosis, autophagy, mitochondrial function, and cellular senescence. Experimental evidence supports its therapeutic potential against cancer, cardiovascular, neurodegenerative, metabolic, and infectious diseases. However, poor aqueous solubility, low oral bioavailability, rapid metabolism, and limited clinical evidence continue to impede its clinical translation. Nanotechnology-based delivery systems, computational modelling, and multi-omics approaches show promise for improving its pharmacokinetic profile and therapeutic efficacy. Bibliometric findings revealed substantial growth in fisetin research, with China leading scientific output and Africa contributing comparatively few publications. Conclusions: Fisetin is a promising multifunctional phytochemical with broad therapeutic potential. Future research should emphasise advanced formulations, rigorous clinical trials, and international collaboration to accelerate its translation into evidence-based clinical practice.