Chronic venous disease (CVD) is a highly prevalent and progressive condition that significantly impairs quality of life and imposes substantial socioeconomic burdens. Despite its widespread impact, CVD remains underdiagnosed and suboptimally managed, particularly in the early stages where timely intervention could prevent progression to debilitating complications such as venous leg ulcers. Current clinical management strategies are largely reactive, focusing on symptom control rather than disease modification. This thesis addresses the critical unmet need for early-stage, evidence-based pharmaceutical interventions through a systematic and multidisciplinary investigation encompassing clinical reviews, epidemiological analysis, and innovative formulation design. The research was structured across five chapters. Chapter 1 provides an overview of chronic venous disease (CVD), tracing the historical development of its recognition and treatment. It also presents the justification for the research, alongside the overarching aim and defined objectives of the study. Chapter 2 presents a comprehensive narrative review of the current clinical approaches to managing CVD and its complications. The review highlights the limitations of existing therapies and identifies the need for pharmacological innovations that target early pathophysiological mechanisms. In Chapter 3, a global systematic review and meta-analysis provide the most extensive prevalence estimates to date for CVD and venous leg ulcers, confirming substantial disease burden, particularly among older adults and females, and revealing geographical and methodological disparities in data reporting. These findings underscore the urgency of developing standardised diagnostic criteria and accessible interventions. Chapter 4 focuses on hesperidin, a flavonoid with demonstrated benefits in CVD management. A systematic review and structured database analysis revealed that while hesperidin is pharmacologically promising, its clinical utility is hindered by poor aqueous solubility, gastric instability, and limited bioavailability. The chapter reviews existing formulation strategies, including complexation, nanocarriers, and pH-responsive systems, while identifying gaps in their translational potential. Chapter 5 forms the experimental core of the thesis, presenting the development of microbiome-triggered, colon-targeted hesperidin formulations. Using a quasi-emulsion solvent diffusion technique, hesperidin was successfully encapsulated within porous microsponges, which were then compressed into core tablets with soya polysaccharide to promote colonic disintegration. Selected core tablets were further coated with a pectin-HPMC shell via powder compression to achieve site-specific release. These formulations were evaluated using in vitro dissolution, microbiome-simulated bioreactor systems, and ex vivo colonic permeation assays. Notably, CS1-400 and CS1-450 emerged as the most effective formulations, demonstrating delayed gastric release, robust microbial biotransformation to hesperetin, and enhanced permeation across porcine colonic membranes. In conclusion, this thesis presents a compelling case for the use of microbiome-responsive, colon-targeted drug delivery systems as an early intervention strategy in CVD. The integration of clinical, epidemiological and pharmaceutical data provides a robust framework for advancing hesperidin-based therapies. The work establishes a strong foundation for future translational research and clinical validation, ultimately contributing to more effective and proactive management of chronic venous disease.