Bioavailability is a critical factor influencing the efficacy of therapeutic agents. Current research has demonstrated that innovative drug delivery systems (DDS) can play a pivotal role in enhancing drug bioavailability. This study aimed to develop and systematically evaluate a range of DDS, including liposomes, nanoparticles, microneedles, and hydrogels, for the delivery of selected therapeutic agents. Therapeutic agents were chosen based on various factors, including solubility, stability, and biological target, and were successfully encapsulated within the DDSs. Comprehensive in vitro characterization of the drug-loaded DDSs was performed, followed by in vivo evaluations in relevant animal models. The study results demonstrated significant improvements in drug bioavailability, as evidenced by enhanced pharmacokinetic profiles and therapeutic outcomes. In addition, the DDSs exhibited excellent biocompatibility and minimal toxicity, reinforcing their suitability for clinical applications. The findings of this study underscore the immense potential of advanced DDSs in improving the bioavailability of therapeutic agents, thereby revolutionizing disease treatment. Continued research and development in this field can lead to the successful translation of these innovative systems into clinical practice, ultimately benefiting patients worldwide.