Background: Wound infection is a manifestation of disturbed host–bacteria equilibrium in a traumatized tissue environment in favor of the bacteria. A wound infection not only has the possibility to elicit a systemic response (sepsis), but is highly likely to inhibit the multiple processes. Materials and Methods: Solid lipid nanoparticles (SLNs) were prepared using glycerol tristearate and poloxamer by solvent evaporation method. The particle size, polydispersity index (PDI), zeta potential (ZP), FTIR, NMR, water vapor transmission rate determination and in vivo wound healing studies were performed. Results: The average particle size results showed that the nanoparticle size of N2 was in the range of 0.4-0.8 µm and polydispersivity index less than 1. The prepared hydrogels had WVTR in the range of 2187.9 g/m2 to 2954 g/m2 could maintain a suitable moist environment in the wound that could enhance the wound contraction and tissue regeneration, thereby accelerating wound healing. Heliotropium indicum extract SLN Hydrogel significantly contributed to wound healing compared with the blank control group at 15 and 18 day post-wounding (P < 0.05). Conclusion: Nanoparticle containing Heliotropium indicum extract could be released slowly from Carboxymethyl chitosan oxidized alginate hydrogel hydrogel in a sustained manner to stimulate fibroblast proliferation, capillary formation and collagen production that can significantly effect on the healing phases. As a result, we suggested that the prepared hydrogel might have great potential application in the wound healing.