Naturally occurring compounds have attracted great attention for drug delivery purposes due to their safety, sustainability, and therapeutic versatility. In particular, an isoflavone with antioxidant and anticancer activity, called genistein, and a biodegradable polymer with superior carrier properties, known as chitosan, have both been proven promising for biomedical applications. However, the low solubility of genistein and the variable absorption profile of chitosan call for new formulation approaches. In this review, the current evidence on various genistein-chitosan combinations is compiled and discussed, considering their bioactive properties, delivery mechanisms, applications in disease management, clinical relevance, regulatory aspects, and future opportunities in targeted drug delivery. Literature indicates that chitosan-based encapsulation of genistein enhances the solubility, stability, and controlled release of the encapsulated genistein, resulting in improved therapeutic activities. Indications include oncology, osteoporosis, wound healing, or neuro, metabolic, and degenerative disorders. New developments in the field of nanotechnology, including liposomal system carriers, micelles, and prodrug methods, have also expanded the formulation possibilities. Regulatory frameworks in major markets prioritize safety, biocompatibility, and quality control, while sustainability and consumer acceptance are emerging as influential determinants of commercialization pathways. The combination of genistein and chitosan represents a paradigm shift in drug delivery, offering a more patient-friendly and environmentally friendly approach. Even with clean preclinical and early clinical data, implementation in routine practice requires strong human testing, standardized regulations, and scalable technologies for product manufacturing.