Plant-derived secondary metabolites represent a reservoir of phytochemicals for regenerative medicine application because of their varied assortment of biological properties including anti-oxidant, anti-inflammatory, antibacterial, and tissue remodeling properties. In addition, bioactive phytochemicals can be easily available, are often more cost-effective in large-scale industrialization, and can be better tolerated compared to conventional treatments mitigating the long-lasting side effects of synthetic compounds. Unfortunately, their poor bioavailability and lack of long-term stability limit their clinical impact. Nanotechnology-based delivery systems can overcome these limitations increasing bioactive molecules’ local effectiveness with reduction of the possible side effects on healthy bone. This review explores new and promising strategies in the area of delivery systems with particular emphasis on solutions that enhance bioavailability and/or health effects of plant-derived phytochemicals such as resveratrol, quercetin, epigallocatechin-3-gallate, and curcumin in bone tissue regeneration.