Objective To observe the efficacy of rehabilitation training coupled with pharmacotherapy on the elderly patients with post-stroke depression (PSD) and its effects on neurological function and cognitive functions. Methods From May 2017 to February 2018, a total of 80 PSD elderly patients were selected for the study, who were treated at the Guangyuan Mental Health Center. The patients were divided into control group and observation group (40 patients each). Both groups were treated with drugs for 8 weeks, and the observation group were given additional rehabilitation training at the same time. The two groups were compared in indices measured before and after treatment, including Hamilton rating scale for depression (HAMD), National Institutes of Health neurological defective scale (NIHSS), stroke-specific quality of life scale (SS-QOL), mini-mental state examination (MMSE) and satisfaction. Statistical analysis was performed using SPSS statistics 13.0, and comparison between the two groups was performed using t test or χ² test. Results Compared with before treatment, HAMD, NIHSS, MMSE and SS-QOL of the two groups were significantly improved after treatment (P<0.05).Compared with the control group, HAMD [(16.22±2.06) vs (19.55±3.12)] and NIHSS [(6.04±1.03) vs (9.68±1.44)] of the observation group were significantly lower after treatment (P<0.05), and MMSE [(23.29±3.38) vs (18.15±3.23)] and SS-QQL [(178.62±3.66) vs (151.58±6.35)] significantly higher (P<0.05). The observation group rated the satisfaction significantly higher than the control group (97.5% vs 85.0%, χ²=3.914, P=0.048). Conclusion Rehabilitation training coupled with medications is effective in the treatment of senile patients with PSD, significantly improving the cognitive and neurological functions and quality of life of the patients, and the paradigm is worth clinical application.