Polyphenols have the potential to prevent many diseases physiologically. This review is a summary of the significance and uses of polyphenols in medicine, pharmaceuticals, nutraceuticals, and dietary supplements. We conducted a systematic review of the literature between 2010 and 2025 based on literature searches online and offline. The Cochrane Risk of Bias tool (RoB 2.0) was used to assess the risk of bias in randomized controlled trials. Consequently, polyphenols (berberine, EGCG (green tea), curcumin, luteolin, lycopene, apigenin, quercetin) are used to treat acute and chronic diseases. Polyphenols have been shown to have anti-cancer, anti-diabetic, anti-inflammatory, anti-analgesic, anti-bacterial, and immunomodulatory properties, making them potential adjuvants for a variety of treatments. A discussion of nanoparticles' pharmacological applications, clinical evidence, safety, bioavailability, toxicity, and prospects will also be included.