This study presents a phyto-nanoengineered bone regenerative platform that addresses the clinical challenges of critical-sized bone defects, which often fail to heal due to impaired regenerative capacity compounded by oxidative stress and chronic inflammation. Traditional interventions, including autografts and synthetic drugs, are limited by poor bioactivity, insufficient tissue integration, and systemic side effects. To overcome these limitations, biologically reduced trans-resveratrol-loaded gold nanoparticles (tRGNPs) were incorporated into a macroporous cryogel scaffold composed of gelatin, chitosan, and nano-hydroxyapatite, forming the tRGCH nano-scaffold. The tRGNPs, synthesized to preserve the bioactive trans-form of resveratrol, exhibited spherical morphology (∼22 nm), high crystallinity, and excellent colloidal stability. They demonstrated potent antioxidant and anti-inflammatory activities by upregulating M2 markers (Arg-1, IL-10) in macrophages while downregulating M1 markers (iNOS, IL-1β). In vitro, tRGNPs significantly enhanced pre-osteoblast proliferation (∼1.5-fold vs. control), migration (95.6 ± 0.3 % wound closure vs. 67.1 ± 0.9 % in control; 1002.7 ± 20.6 migrating cells/mm² vs. 132.3 ± 21.2 in control), and osteogenic differentiation, achieving ALP activity and calcium deposition comparable to osteogenic induction medium, while mitigating oxidative stress-induced damage. Furthermore, the pre-synthesis incorporation of tRGNPs ensured homogeneous nanoparticle distribution, improved mechanical integrity, and sustained biomolecular release, effectively addressing issues such as polyphenol instability and burst release. The resulting tRGCH scaffolds exhibited optimal swelling, biodegradability, and porosity, closely mimicking native bone matrix architecture. In a rat tibial defect model, tRGCH scaffolds significantly enhanced bone regeneration, inducing collagen formation (∼36 % trichrome-positive area compared to control), mineral deposition, and trabecular organization. This nanoengineered system offers a promising, cost-effective approach for bone regeneration under inflammatory conditions.