Cerebral ischemia–reperfusion (I/R) is a kind of neurovascular disease that causes serious cerebral damage. MicroRNAs (miRNAs) have been widely reported to participate in multiple diseases, including cerebral I/R injury. However, the exact mechanisms of miR-7-5p in cerebral I/R injury was not fully elucidated. In this study, we explored the biological role and regulatory mechanism of miR-7-5p in cerebral I/R injury. We established an in vivo model of cerebral I/R by middle cerebral artery occlusion and an in vitro cellular model of cerebral I/R injury through treating neurons (SH-SY5Y cells) with oxygen-glucose deprivation (OGD). In addition, miR-7-5p expression was confirmed to be upregulated in the cerebral I/R rat model and OGD/R-treated SH-SY5Y cells. Moreover, miR-7-5p inhibition overtly suppressed cerebral injury, cerebral inflammation, and SH-SY5Y cells apoptosis. Sirtuin 1 (sirt1) is previously reported to alleviate I/R, and in this study, it was identified to be a target of miR-7-5p based on luciferase reporter assay. Reverse transcription-quantitative polymerase chain reaction revealed sirt1 expression was downregulated in the cerebral I/R rat model and OGD/R-treated SH-SY5Y cells. Besides, miR-7-5p negatively regulated sirt1. Finally, rescue assays delineated sirt1 overexpression recovered the miR-7-5p upregulation-induced promotion on cerebral I/R injury. In conclusion, miR-7-5p enhanced cerebral I/R injury by degrading sirt1, providing a new paradigm to investigate cerebral I/R injury.