For over a decade, dexamethasone (DEX) has been used for bone regenerative and anti-inflammatory purposes. It has also shown promise for inducing bone regeneration by using it as component of osteoinductive differentiation medium, particularly forculture models. Despite its osteoinductive properties, its use is limited due to its associated cytotoxicity, particularly when used at higher concentrations. DEX has adverse effects when taken orally; thus, it is best to use it in a targeted manner. Even when given locally, the pharmaceutical should be distributed in a controlled manner based on the needs of the wounded tissue. However, because drug activity is assessed in two-dimensional (2D) circumstances and the target tissue is a three-dimensional (3D) structure, assessing DEX activity and dosage in a 3D milieu is critical for bone tissue development. The current review examines the advantages of a 3D approach over traditional 2D culture methods and delivery devices for controlled DEX delivery, particularly for bone repair. Further, this review explores the latest advancement and challenges in biomaterial-based therapeutic delivery approaches for bone regeneration. This review also discusses possible future biomaterial-based strategies to study efficient DEX delivery.