Chrono-therapeutics tries to adapt therapies to 24-hour rhythms, which come about as a result of the circadian timing system's regulation of the majority of biological functions. In order to achieve maximum healing perfection by using Nano lipid-carried nutraceuticals with orchestrating between healing phases of honey and growth factor in modulating their concentration and profiling of metabolomics fact of wound healing during treatment, a more novel chrono-pharmacological statement of Nano lipid application in a different time is required. Chronopharmaceutical possible to optimize pharmacotherapeutics while taking into account rhythm dependencies in the kinetics and dynamics of drugs, which is predicted in temporal variability for skin and wound healing. Patients and Methods: Twenty-five rabbits were endorsed in the present study divided into five groups. The full excisional wounds were treated with different formulas, control group and SNLHoney & PDGF treated groups which were divided according to effective concentration EC50 and EC20 as follows (EC50Honey 11.97 & EC50PDGF 0.38, EC50Honey 11.97 & EC20PDGF 0.08, EC20Honey 1.16 & EC50PDGF 0.38, and EC20Honey 1.16 & EC20PDGF 0.08%) respectively, as a daily dressed treatment. The linear closure rate of wound healing t½ and closure velocity were measured, choosing the best effective concentration of honey and PDGF. After that, fifty rabbits were divided according to the treatment diurnal time (7, 15, and 23) into four major groups: control, SNL-blank, conventional EC50Honey & EC20 PDGF, and SNL EC50Honey & EC20 PDGF. Results: The outcomes of wound healing demonstrated the quality and extent of synergism between the effective concentrations of SNLHoney and PDGF. Also, compared to conventional and SNL-blank forms, the chrono-therapeutic challenge of synergistic SNLHoney and PDGF lowered wounds and was faster healed. In addition to the fold changes of metabolomes in Chrono protocolled treated groups of skin wound healing Succinic acid 0.86, Fumaric acid (Dimethyl fumarate) 1, beta-Sitosterol acetate 1, 2-Deoxy-D-galactose 1.28, Proline 1, Arginine 1.06, Adenosine 1, Xanthine (Purin-2,6-dione) 2.6, alpha Tocopherol 1, and Phosphoramidic acid 1, the diagnostic markers of metabolomes, in dosed during a significant appearance or disappearance and increase or decrease metabolomes fractions determined according to groups marker differentiation between treated groups: control and SNL-Blank Succinic acid and Fumaric acid (Dimethyl fumarate), SNL-Blank and conventional beta.-Sitosterol acetate and 2-Deoxy-D-galactose, and conventional and SNLHoney and PDGF Proline, Arginine, Adenosine, Xanthine (Purin-2,6-dione), alpha Tocopherol, and Phosphoramidic acid. Conclusion: The combination of SLNHoney& PDGF according to effective concentration increased of synergism of honey and PDGF and therefore accelerated wound healing. The Chrono-therapeutic effect led to optimized results to increase the efficiency of the therapeutic effect via utilizing circadian rhythm through identifying a class of biomarkers that correspond to wound healing processes.