In a world pivoting toward integrative and personalized medicine, Boerhavia diffusa L. (Punarnava) emerges as a phytopharmacological gem bridging ancestral knowledge with 21st -century drug discovery. Celebrated in Ayurveda for revitalizing organs and restoring systemic balance, this resilient herb holds untapped potential for treating complex disorders like inflammation, diabetes, and renal dysfunction. This review offers a multidimensional exploration of its traditional wisdom, biochemical depth, and modern translational relevance. A transdisciplinary approach was employed, analyzing peer-reviewed databases for ethnomedical documentation, bioactive profiling via advanced spectroscopy (LC-MS/MS, FTIR, NMR), and pharmacological insights from in vitro, in vivo, and emerging in silico models. Novel formulation strategies—including nanocarriers, phytosomes, and hybrid herbal scaffolds-were examined for enhancing bioavailability, targeting, and therapeutic index. Boerhavia diffusa hosts a dynamic phytochemical matrix-punarnavine, boeravinones, ursolic acid, and flavonoids that act as polypharmacological agents. These modulate redox signaling, immune checkpoints, and metabolic enzymes, offering renoprotective, hepatoprotective, antidiabetic, and cytoprotective effects. Smart delivery systems-nanogels, biopolymer conjugates, and green-synthesized nanoparticles-amplify its efficacy and reduce toxicity. Bioinformatics tools and molecular docking studies further reveal promising interactions with key therapeutic targets, inviting new drug leads from this traditional herb. Boerhavia diffusa is more than a medicinal plant-it's a biointelligent system with vast therapeutic implications. To harness its full potential, the roadmap ahead must integrate omics-driven validation, AI-assisted drug design, and eco-sustainable cultivation practices to elevate this ancient remedy into a global therapeutic asset.