Background: This study aims to explore the clinical effect of psychotherapy based on five-element theory in traditional Chinese medicine (TCM) in improving the mental states of patients with post-stroke depression (PSD), to provide reference and guidance for clinical treatment. Methods: A retrospective study was conducted on 163 PSD cases treated in The Second Affiliated Hospital, Hengyang Medical School, University of South China from January 2022 to January 2023. The patients treated with conventional treatment were included in the control group (n = 84), and patients receiving psychotherapy based on five-element theory in TCM and conventional treatment were classified as the observation group (n = 79). The anxiety levels, depression levels, TCM syndrome scores and sleep quality were compared in both groups. The enumeration data were tested by χ2 test. Kolmogorov-Smirnov method tested whether the measurement data met normal distribution, and those did not meet normal distribution were tested by Mann-Whitney method. The difference was statistically significant at p < 0.05. Results: After 4-week and 8-week treatments, the observation group had significantly lower scores of Hamilton Anxiety Scale (z = –4.562, –6.765; p < 0.001), Hamilton Depression Scale (z = –7.588, –8.023; p < 0.001), TCM syndrome (z = –7.138, –10.946; p < 0.001), and Pittsburgh sleep quality index (z = –6.819, –8.240; p < 0.001) than the control group. Conclusion: Psychotherapy based on five-element theory in TCM is beneficial to patients with PSD and can bring a certain clinical reference value.