Objective To investigate the clinical effect of butylphthalide combined with urinary kallidinogenase in the treatment of chronic cerebral circulatory insufficiency (CCCI). Methods A total of 102 CCCI patients admitted to our hospital from October 2020 to December 2021 were retrospectively enrolled in this study. According to the different therapeutic strategy, the patients were divided into combined group (treated with butylphthalide combined with urinary kallidinogenase, n = 51) and butylphthalide group (treated with butylphthalide, n = 51). Blood flow velocity and cerebral blood flow perfusion before and after treatment between the two groups were compared. The clinical efficacy and adverse events of the two groups were analyzed. Results After treatment, the effective rate of the combined group was significantly higher than the butylphthalide group ( p = .015). Before treatment, the blood flow velocity of middle cerebral artery (MCA), vertebral artery (VA), basilar artery (BA) were comparable ( p > .05, respectively), while after treatment, the blood flow velocity of MCA, VA, and BA in combined group were faster than those in butylphthalide group ( p < .001, respectively). Before treatment, the relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), relative mean transmit time (rMTT) of the two groups were comparable ( p > .05, respectively). After treatment, rCBF and rCBV in combined group were higher than those in butylphthalide group ( p < .001, respectively), and rMTT in combined group was lower than that in butylphthalide group ( p = .001). The rate of adverse events in the two groups were comparable ( p = .558). Conclusion Butylphthalide combined with urinary kallidinogenase can improve the clinical symptoms of CCCI patients, and the effect is promising, which is worthy of clinical application.