Background and aim: In this study, an attempt has been made to investigate the clinical efficacy of nano-hydrogel (0.2%) embedded with oleic acid and quercetin in comparison with the results of nano-hydrogel (0.2%) alone in the treatment of diabetic foot ulcers in diabetes mellitus patients. Method: The current study was a randomized clinical trial study in 200 diabetic patients with diabetic foot ulcers referred to Amir-ol-momenin Hospital in Savad Kuh, Mazandaran, Iran during the years 2021 to 2022 were divided into two intervention groups (nano-hydrogel) by random sampling method and based on the inclusion criteria (0.2%) embedded with oleic acid and quercetin) and control group (hyaluronic acid (2%) alone) were divided (100 patients in each group). Statistical analysis was done with SPSS software version 23. Differences with p-value<0.05 were considered significant. Both groups received topical treatment daily for two months. Follow-up was done every week for six months from the beginning of the study. Result: The mean pain in the intervention group (2.12±0.95) was significantly lower compared to the control group (4.72±1.34) (p<0.01). 64 patients in the intervention group and 31 patients in the control group experienced complete healing with a shorter average time (p>0.05). Conclusion: The present study showed that the use of nano-hydrogel (0.2%) embedded with oleic acid and quercetin can significantly reduce the recovery period compared to nano-hydrogel (0.2%) alone; It also significantly reduced the amount of pain.