Objective To explore the efficacy and mechanism of low molecular weight heparin calcium combined with α-lipoic acid in the treatment of diabetic foot. Methods A retrospective analysis of 89 diabetic foot patients who received treatment in our hospital from 2019 to 2022 was divided into observation group (44 cases) and control group (45 cases) according to different treatment methods. Above, the control group was treated with α-lipoic acid, the observation group was treated with low molecular weight heparin calcium combined with α-lipoic acid. The TcPO2 value, the blood flow velocity and radius of the dorsal artery of the foot, the changes of serum indexes, the ulcer area, wound granulation, clinical efficacy and adverse reactions were compared between the two groups before and after treatment. Results After treatment, the TcPO2 values of the two groups of patients were lower than those before treatment, and the observation group was significantly lower than the control group (P<0.05). After treatment, the observation group was significantly higher than the control group (P<0.05). Before treatment, there was no significant difference in serum IL-6, MMP-2 and MMP-9 between the two groups (P>0.05). After treatment, the levels of each index in the observation group were lower than those in the control group (P<0.05). After treatment, the improvement of ulcer area and wound granulation in the observation group were better than those in the control group, and were comparable (P<0.05). The total effective rate of clinical treatment was higher than that of the control group (P<0.05). The incidence of adverse reactions in the observation group was compared with that in the control group (P>0.05).Conclusion The combined intervention of low molecular weight heparin calcium and α-lipoic acid in diabetic foot patients is beneficial to improve extremity ischemia, increase foot blood circulation, promote wound healing, and improve clinical treatment effect, and has fewer adverse reactions, which is worthwhile of clinical promotion and application