Objective: To investigate the effects of Lokomat robot-assisted gait training (RAGT) on lower limb motor function and cerebral hemodynamics in patients with severe hemiplegia based on conventional rehabilitation therapy. Methods: A total of 126 patients with severe hemiplegia were selected and divided into a control group (conventional rehabilitation therapy, n=69) and an observation group (conventional rehabilitation plus RAGT training, n=57) according to different rehabilitation methods. After propensity score matching, each group included 44 cases. Cerebral hemodynamics-related indicators, balance function and lower limb motor function scores, gait parameters, levels of angiopoietin-1 (Ang-1) and vascular endothelial growth factor (VEGF), and cerebral hemodynamics indicators including maximum blood flow velocity (Vmax), minimum blood flow velocity (Vmin), peripheral resistance (RV), and dynamic resistance (DR) were compared before treatment, at 2 weeks, and at 5 weeks of treatment. A difference-in-differences (DID) model was constructed to analyze changes in vascular active substances and cerebral hemodynamics indicators after treatment in patients with severe hemiplegia. Results: After treatment, the observation group showed higher scores than the control group in the Berg Balance Scale (P<0.001), Fugl-Meyer Assessment (P<0.001), Stroke Rehabilitation Motor Function Assessment Scale (P<0.001), as well as faster walking speed, longer step length, and higher step frequency (P<0.05). Ang-1 and VEGF levels in the observation group were higher than those in the control group (P<0.001). Vmax and Vmin were higher than in the control group, while RV and DR were lower than in the control group (P<0.05). DID model results showed that the group×time interaction had a significant effect on improving vascular active substances and cerebral hemodynamics indicators (P<0.05). Conclusion: On the basis of conventional rehabilitation therapy, adjunctive RAGT training has a favorable clinical therapeutic effect, significantly optimizes cerebral hemodynamics in patients with severe hemiplegia, promotes the secretion of substances related to angiogenesis, and markedly improves patients’ balance ability, lower limb motor function, and gait parameters.