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The advancement of natural-based biomaterials in providing a carrier has revealed a wide range of benefits in the biomedical sciences, particularly in wound healing, tissue engineering and regenerative medicine. Incorporating nanoparticles within polymer composites has been reported to enhance scaffolding performance, cellular interactions and their physico-chemical and biological properties in comparison to analogue composites without nanoparticles. This review summarized the current knowledge of nanoparticles incorporated into natural-based biomaterials with effects on their cellular interactions in wound healing. Although the mechanisms of wound healing and the function of specific cells in wound repair have been partially described, many of the underlying signaling pathways remain unknown. We also reviewed the current understanding and new insights into the wingless/integrated (Wnt)/β-catenin pathway and other signaling pathways of transforming growth factor beta (TGF-β), Notch, and Sonic hedgehog during wound healing. The findings demonstrated that most of the studies reported positive outcomes of biomaterial scaffolds incorporated with nanoparticles on cell attachment, viability, proliferation, and migration. Combining therapies consisting of nanoparticles and biomaterials could be promising for future therapies and better outcomes in tissue engineering and regenerative medicine.