Phytoconstituents derived from medicinal plants have gained significant attention due to their diverse pharmacological activities and therapeutic potential in the management of various diseases. However, despite their promising bioactivity, many phytoconstituents suffer from poor pharmacokinetic profiles, including low aqueous solubility, limited permeability, and instability in the gastrointestinal environment, rapid metabolism, and extensive first-pass elimination. These limitations result in reduced bioavailability and hinder their clinical translation. The complexity of plant-derived compounds, along with variability in chemical composition and physicochemical properties, further complicates their absorption and systemic distribution. To overcome these challenges, several advanced strategies have been developed, including the use of nanotechnology-based drug delivery systems such as solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, and nanoemulsions. Additionally, lipid-based formulations, phytosomes, prodrug approaches, and the use of permeation enhancers have shown considerable promise in improving the pharmacokinetic behavior of phytoconstituents. Recent advancements in formulation science, computational modeling, and pharmacokinetic optimization have contributed to enhancing the therapeutic efficacy of plant-derived bioactives. This review aims to provide a comprehensive overview of the pharmacokinetic challenges associated with phytoconstituents and highlights the innovative strategies employed to improve their bioavailability and clinical applicability