Purpose. We aimed to evaluate and compare the efficacy of neem leaves extract with normal saline irrigation practice in wound dressing on healing outcome and clinic-physiological parameters among individuals with diabetic foot ulcer (DFU). Methods. A quasiexperimental with repeated measures design was used on two study groups. One group received neem leaf extract wound irrigation and another group received normal saline wound irrigation. Study participants were randomly assigned to each group from 100 DFU individuals. Demographic and clinical data sheets were used to collect baseline information. Random blood sugar and HbA1C measurement was performed on the initial day of visit for all participants. We used the PUSH tool for wound assessment (wound surface area, exudate amount, and tissue type), and clinic physiological parameters (temperature, pulse rate, respiration, blood pressure, wound pain, wound infection, and local warmth) assessment was performed at baseline and then at the end of each week till four weeks were completed. Participants attended a foot clinic every 3rd or 4th day for wound care. Results. Reduction of wound healing score (PUSH score) and other wound variables improved significantly in the neem leaves extract group (p<0.001). There were no significant changes in the clinic-physiological parameters. Conclusion. Neem leaves extract irrigation for foot ulcers is considered to be very safe as it did not cause any complication systematically during the study. Neem leaf extract solution can be used as an alternative solution for normal saline. Managing DFU requires continuous foot care and early risk identification of ulcer. © 2021 Muthu Srinivasan Jayalakshmi et al.